Highly efficient and switchable chirality transfer between protein and achiral plasmonic assemblies

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Therefore, investigating the chirality transfer from abundant biomolecules to simple nanostructures without sophisticated three-dimensional nanofabrication is convenient and meaningful. However, in the previous studies with this goal, the biomolecules mostly acted as structurally chiral templates to permanently break the mirror symmetry of nanostructures, whose chirality transfer was irreversible and thus lacking in flexibility in applications. Here we discovered an in-situ biomolecule-stretching strategy to realize the highly efficient (dissymmetry factor 0.2) and reversible chirality transfer from biomolecules to nanoparticles for the first time, based on a Coulombic “field effect” rather than a traditional “structural effect”. Due to this unique “field effect”, the mirror symmetry of nanostructures is well maintained. Thus, the chirality can be smartly reversed over 100 cycles to meet various requirements of modern chiral devices. Our results unravel how achiral plasmons acquire chirality from a biomolecule efficiently and reversibly, interpreting the intimate interaction between biomolecules and plasmonic fields. Physical sciences/Materials science/Nanoscale materials/Metamaterials Physical sciences/Nanoscience and technology/Nanobiotechnology/Biosensors Physical sciences/Materials science/Biomaterials/Biomaterials – proteins Chirality transfer chirality switching high g-factor biomolecule colloidal assembly Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Nature creates chiral biomolecules to support corresponding biological processes 1 . Various kinds of biomolecules occupy a big family in molecular chirality. While at nanoscale, when chirality meets plasmonic nanostructures, intense circular dichroism (CD) in the visible-near-infrared range is generated, which is stronger than the (bio)molecular CD that are usually located in the ultraviolet (UV) range. Harnessing this, chiral plasmonics gives access to powerful polarization control and enantiomer sensing/catalysis 2-5 . Nowadays, helical 6-9 and scissor-like 10-13 chiral nanostructures can be realized through DNA origami or lithographic methods. Nevertheless, the fabrication of artificial chiral nanostructures is significantly more onerous. That is why recently researchers have endeavored more and more in transferring the effortless biomolecular chirality to plasmonic nanostructures 5-7 . In the pioneering studies with this goal, biomolecules act as a template to direct the plasmonic nanostructure into a chiral shape, where the chirality transfer is irreversible. Thus, the question arises: is it possible to transfer (bio) molecular chirality efficiently and reversibly to plasmonic nanostructures? It remains one of the holy grails in light matter interaction, as it could open a dynamic new world of plasmonic chirality independent from the tedious fabrication of sophisticated nanostructures. Plasmon-coupled CD (PCCD) provides the possibility of the reversible chirality transfer, as it transfers the molecular chirality electrostatically onto the achiral nanostructures without breaking of symmetry 14-21 . Put differently, the dipole/multipole of a chiral molecule can electrostatically induce a chiral response on the achiral plasmonics, where the biomolecule is an interaction host rather than a chiral template. However, PCCD is usually too weak and is inversely proportional to the distance between chiral molecule and plasmonic nanostructure 14,15 . Accordingly, up to date people have put most efforts in accommodating the chiral molecules into various kinds of narrow nanogaps 16-21 , which provide plasmonic hotspots to enhance PCCD while ensuring molecules and nanostructures in close range. Even so, the state-of-the-art of PCCD is still far from an efficient chirality transfer, which is much lower than the structurally transferred CD. Other factors should also be considered besides plasmonic hotspots. For example, similar efforts regarding the (bio)molecular side are much more limited 18 , mainly because most molecule-nanostructure complexes are static, which makes it difficult to probe the molecular component and monitor the induced changes in PCCD. However, as biomolecules are the chiral chromophores in PCCD, understanding the molecular side and optimizing it may lead to a leverage effect on signal amplification. The prerequisite for investigating the molecular aspects—to better understand the transfer mechanism and efficiently transfer more intense CD from biomolecules—is the realization of smarter nanostructures that allow researchers to easily deform and probe the molecules in real time. Construction of stretchable 1D linear nanoparticle-protein complex array stipulating pure PCCD To address this, we designed a structurally non-chiral one-dimensional (1D) linear chain array of Au nanospheres conjugated to bovine serum albumin (BSA) with an average diameter of 70.6 nm (Extended Data Fig. S1) based on a template-assisted colloidal self-assembly strategy 22-25 . These single nanospheres carrying BSA imparted negligible PCCD that can hardly be detected 11 due to the lack of plasmonic hotspots and structural asymmetry (Extended Data Fig. S2). Arranging such single-crystalline spherical building blocks in a 1D linear assembly enables us to completely exclude structural chirality, thus rendering the BSA molecules as the sole origin of chirality (Fig. 1a and Extended Data Fig. S2). At the same time, the high-density plasmonic hotspots in the assembly promote the collective PCCD to an amount that can be detected by common ensemble spectroscopy (~ 50 mdeg, grey line in Fig. 2a), which owns the opposite handedness to the molecular chirality of BSA in the UV region (see the full CD spectrum in Extended Data Fig. S3). While, a 1D linear assembly of Au nanospheres conjugated to polyethylene glycol (PEG) showed no CD signal due to the achirality of the PEG molecules, thus confirming the achirality of the 1D chain nanostructure (Extended Data Fig. S2). Furthermore, as a thin adhesive layer of polyethylenimine (PEI) cast onto polydimethylsiloxane (PDMS) substrate (in which the nanospheres are partially embedded for ~20 nm, 29%) 22 acts as a matrix to transfer the strain from the substrate to the nanospheres and thus also to the proteins bridging the nanospheres. Hence, stretching the soft elastomeric PDMS substrate gradually (Fig. 1b) allows the stretching of the proteins bridging the nanospheres. With increasing strain along the nanosphere chain direction, atomic force microscopy (AFM) images indicated that the nanospheres are gradually separated (Fig. 1c-e and Extended Data Fig. S4). Simultaneously, the bridged tangled proteins are re-conformed from a random oriented state to an aligned state and later even to a stretched state, providing us with a model system that allows to access a range of chiral molecular conformations, and to systematically investigate the underlying mechanism of chirality transfer from biomolecules to plasmonic fields. Anomaly PCCD leap during stretching and its superb reversibility When the external strain is gradually increased from 0% to 55%, the nanosphere chain split into oligomers, within which the interparticle nanogaps enlarge gradually (Fig. 1c-e and Extended Data Fig. S4). In the state-of-the-art theory, the contribution PCCD should rapidly decrease because the nanosphere-molecule center-to-center distance increases and the plasmonic hotspots weakens simultaneously. While by contraries, the collective PCCD increases drastically by a factor of up to 22 (Fig. 2a-b). The observed collective PCCD intensity reached up to 1.36 deg at a wavelength of ~700 nm with a g-factor of 0.2 (Fig. 2a and Extended Data Fig. S5). Both the obtained intensity and g-factor are between 10 and 1000 times greater than those previously observed PCCD (Extended Data Table S1), and the achieved CD strength and g-factor are comparable to or even higher than conventional structural CD. Therefore, the stereotype of low efficiency of PCCD has been completely broken. PCCD is highly sensitive to the external strain along the nanosphere chain direction. The increasing tendency of the strain-induced PCCD leap shows a non-linear trend: After an initial phase with a linear increase, the gradient is decreasing at about 25%, until a plateau is reached at about 55% strain as plotted in Fig. 2b. Upon release, the system returns to the initial low PCCD value. The stretching process is continuous and highly stable, allowing control of the PCCD using strain as an external stimulus with an outstanding cycling stability: Even after 100 cycles from 0% to 50% strain (Fig. 2d), the high modulation contrast is retained only with a slight drop of CD intensity (~ 4%). But when the assembly was immersed into water overnight, the CD intensity self-healed to original due to the re-intertwined protein segments. Most chiral nanostructures are 3D or quasi-3D, which means that chiral tuning also requires a structural deformation in multiple dimension 10-13 . In contrast, in our 1D assembly the deformation in just one dimension is sufficient to powerfully tune the chirality of the whole plasmonic structure. This reduction of dimensionality enables a much simpler and more robust chirality switching. Monitoring of the plasmonic properties of the nanoparticle-protein complexes during stretching As PCCD results from the interaction between plasmonic modes and molecular chirality 14,15 , both contribute simultaneously to PCCD as a whole. So far, research efforts have focused on the plasmonic side, showing that stronger hotspots generate stronger PCCD 14-21 . But our results above validated that something beyond the plasmonic side plays a leverage effect on PCCD. To make it clearer, we first examined the changes of the plasmonic properties of the 1D chiral array during the stretching process (Fig. 3a). The 1D linear NP chain array has two plasmonic peaks in the extinction spectra (marked by the green and orange dotted lines, Fig. 3a), representing the transversal and longitudinal plasmonic modes respectively. From the extinction spectra during stretching, we can see that the difference in extinction between left-handed circularly polarized (LCP) light and right-handed circularly polarized (RCP) light mainly originates from the longitudinal mode 19 , indicating that mainly the BSA molecules located between the nanospheres contribute to the collective PCCD. While the peak position of the transversally dominated mode stays nearly constant, together with an increasing extinction intensity. As for the longitudinally dominated mode, it experiences a slight blue-shift, implying the splitting of the nanosphere chain and the weakening of the plasmonic hotspots upon strain. The sharpening of both plasmonic peaks during stretching indicates the more centralized oligomer length distributions during stretching (Fig. 1f). The decrease of the electric field enhancement in the hotspots was further traced by surface-enhanced Raman scattering (SERS) measurements of the 1D assembly during stretching, as shown in Fig. 3b, c. The sample as it is, without stretching, shows typical contributions from phenylamine (Phe) (1004, 1030 and 1080 cm -1 ) with weaker signals at 914, 955, 1100 and 1168 cm -1 , due to lysine (Lys) 26 . The Phe contribution is expected due to both its large percentage in the composition of BSA and its large Raman cross-section as compared with the rest of the amino acids 27 . In the case of Lys, the weak bands observed are consistent with its large concentration in BSA. Notably, upon stretching two phenomena occur. First, some of the SERS signals, those related to Lys disappear; and second, while in the case of Phe the bands continue to be present, their absolute intensity decreases with stretching, with an additional change in their relative intensity. Simultaneously, the disappearance of the signal of Lys and the exponential decrease of the signal of Phe upon stretching can be explained by the strain-induced enlargement of the intergap size in the nanosphere chain assembly (Fig. 1d). As this gap enlarges, the energy of the electromagnetic hotspot formed by the plasmon intercoupling between two neighbor particles exponentially decrease with the subsequent decrease in the SERS intensity (Fig. 3c) 28 . On the other hand, the changes of the relative intensity in the Phe signals clearly point towards to Phe reorientation as the protein is stretched 29,30 , as a clear demonstration of the surface selection rules 31 . Therefore, concerning the plasmonic side, the hotspots were indeed weakened during stretching. However counterintuitively, we observed a strong PCCD increase, indicating that strain-induced reformation from the molecular side plays a much more important role than the plasmonic hotspots. How a biomolecule reversibly turns an achiral nanoparticle strongly chiral It is very interesting that the chiral molecules in the assembly only represent a small fraction of the ensemble (theoretically only few BSA molecules could fit in a gap according to the gap volume) 19 , but upon stretching have such a large effect on the PCCD. To decode this, we have to zoom in on the structural arrangement: When the Au@BSA nanospheres are assembled in the PDMS wrinkles and drying, the nanospheres get close and the segments of adjacent BSA shells tangle with each other due to the capillary force (Extended Data Fig. S1). After drying, the BSA molecules in the gaps of nanosphere chains shrink and present a random globular state (Fig. 4a, left panel). As the protein structure is abundant in both rigid α-helices and flexible random coils, BSA can also be stretched upon strain by pulling the random coils, while the rigid α-helices which mainly feature the dipoles, become more aligned along the direction of strain (Fig. 4a, right panel), increasing the collective dipoles of BSA. Accordingly, we infer that the strain-induced stretching of the BSA molecules is intimately connected to the observed PCCD leap. This raises a fundamental question: Why would the stretching of a chiral molecule sharply enhance the PCCD? We know PCCD is based on the electrostatic interaction between a chiral molecular dipole and plasmonic bands; a stronger molecular dipole will thereby induce a more chirally polarized plasmons 14,15 . Additionally, for a molecular dipole, the parallel alignment to the interparticle axis is favored to PCCD compared with the perpendicular or even random orientation, since the CD signal proportionally scales to the dipole moments along the interparticle axis 14,15 . During the stretching process, the BSA molecules bridging the nanospheres are tightly stretched and elongated, resulting in a rising parallel molecular conformation with regard to the particle axis (Fig. 4a). Furthermore, the stretching of a chiral molecule may result in an increase of the effective dipole length, which will also increase the collective molecular dipole of a chiral molecule (Fig. 4a). Enhanced molecular dipole by stretching thus results in the ultrastrong chiral pattern on the achiral nanospheres and achieve the PCCD leap. Electromagnetic simulations were performed to confirm the enhanced PCCD effect. Rotation of the simulated dipole of a chiral molecule by 90° results in a drastic drop of the differential extinction (Fig. 4b), exhibiting that a head-to-head orientation of molecular dipole is preferred in PCCD. Furthermore, holding on this preferred orientation, simulations show that the effect can be even more pronounced if the particle spacing remains unchanged and only the molecular dipole is strengthened (Fig. 4c). The simulations of electric field (Fig. 4d) of the nanosphere assembly present the plasmonic hotspots along the chain direction. While the simulation of surface charge distribution (Fig. 4e) shows the electrostatic interaction in the gaps for PCCD between chiral molecules and plasmons. The simulation can well match our experimental results and help to confirm the huge impact of molecular conformation on PCCD enhancement. Summary and outlook Our stretching-molecule strategy realized the efficient and reversible chirality transfer between molecular scale and nanoscale for the first time, overcoming the size-mismatching of the two interacting components and the intense dependence of strong plasmonic hotspots. It will promote convenient and ultrastrong plasmonic chirality consisting of biomolecules and arbitrary achiral nanostructures, enabling the directly borrowed plasmonic chirality from natural molecules. Notably, due to the unique electrostatic interaction between biomolecules and achiral nanoparticles, this chirality transfer can be dynamically reversed for over 100 times, providing guidance for the design of smart chiroplasmonic nanocomposites for biosensing and optoelectronics. The stretching-molecule strategy can also be achieved by many other stimuli other than the mechanical strain in this work, for example solvents, pH, light, electric and temperature that can increase the dipole of the chiral molecule. Therefore, our stretching-molecule strategy is versatile for tailoring various smart CD devices without sophisticated 3D nanofabrication. We anticipate our assay to be a starting point for showing the giant protein power when interacting with plasmonic nanostructures. Only a stretch of protein will stir the plasmons tremendously. This could also in turn allow sensing mechanical properties of proteins (e.g., conformation and unfolding energetics) under strain through the robust plasmonic CD at a level of few or even single molecules. Biomolecules are an important part of nature and the more we know about them and the underlying chirality transfer mechanism, the more we can communicate with nature. Materials and Methods Chemicals. Hydrogen tetrachloroaurate (HAuCl 4 , >99.9%), sodium borohydride (NaBH 4 , 99%), L-ascorbic acid (AA, C 6 H 8 O 6 , >99%), bovine serum albumin (BSA, 98%), hexadecyltrimethylammonium chloride (CtaC, 25 wt % in water), and polyethylenimine (PEI, Mw 2 kg/mol, linear, 50 wt% in water) were purchased from Sigma-Aldrich. Hexadecyltrimethylammonium bromide (CtaB, 99%) was supplied by Merck KGaA. Sodium hydroxide (NaOH, 1 M) solutions and trisodium citrate (Na 3 C 6 H 5 O 7 , >99%) were received from Grussing. Sylgard 184 PDMS elastomer kits were purchased from Dow Corning. All chemicals were used without further purification. High-purity deionized water (18.2 MΩ cm -1 ) was used in all aqueous preparations. Synthesis and functionalization of single-crystalline nanospheres. The Au nanospheres were synthesized, as reported previously, followed by a ligand exchange process to a BSA/PEG coating 22 . First, 2 nm Au seeds were prepared through reduction of HAuCl 4 using NaBH 4 with CtaB as stabilizer. Further the Au seeds were twice grown in solution (containing HAuCl 4 , ascorbic acid and CtaC) to a final diameter of ~70.6±1.2 nm. Additionally, in the last growth step, a syringe pump system was invoked to ensure kinetic control of Au growth. The final product was collected by centrifugation and washed twice with a 2 mM CtaC solution. Finally, the CtaC stabilizers could be readily exchanged with either chiral ligands such as BSA 22 or achiral ligand such as PEG 32 . Large scale 1D nanosphere assembly. The wrinkled templates with a wavelength and amplitude of ~370 nm and ~35 nm, respectively, were obtained according to the previously published procedure. PDMS was prepared by casting the mixed cross-linker/prepolymer mixture (1:5, Sylgard 184, Dow Corning) in a leveled polystyrene dish and then by degassing in a vacuum. The PDMS mixture was cross-linked at 80 °C with a final thickness of ~2 mm. The cured PDMS was cut into 1 × 4.5 cm 2 strips. To achieve PDMS wrinkles, these strips were fixed in a home-built stretching device and elongated by 40%. The elongated PDMS strips were then O 2 -plasma-treated (Flecto 10, Plasma Technology) for 120 s (100 W, 0.3 mbar O 2 ). The plasma-treated PDMS strip was then cooled to RT and slowly released. The obtained PDMS wrinkling was cut into 1 × 1 cm 2 stripes as templates to guide the nanospheres into closely packed 1D linear assemblies by spin-coating as previously reported. Three microliters of Au nanosphere suspension ([Au 0 ] = 12 mg/mL, pH 11) was spread onto the PDMS wrinkled template, followed by a two-stage spin-coating process (30 s at 1500 rpm, and 30 s at 4000 rpm, photoresist spinner, Headway Research Inc.). After drying, the assembly took on a rose/grey color with angle-dependent anisotropy. The 1D nanosphere assemblies trapped inside the PDMS wrinkles were then wet-transferred onto a flat PDMS substrate for better optical performance. The target PDMS with a cross-linker/prepolymer mixing ratio of 1:15 was cured as above. Subsequently the target PDMS substrate was incubated with a 10 mg/mL PEI solution for 3h to apply an adhesion layer on top, promoting complete transfer of the nanosphere assemblies. For the wet transfer, a droplet of water (pH 9) was placed on the center of the target PDMS substrate. With a pressure of 100 kPa the nanosphere-filled PDMS stamp was pressed onto the target PDMS. After drying and detaching, the 1D nanosphere chains were transferred to the flat PDMS substrate. In contrast, PEG-coated nanoparticles were directly assembled on PDMS stripes by confinement assembly technique 33 . For this the target PDMS was prepared and hydrophilized as described above. Four microliters of the PEG coated nanoparticles were placed on the hydrophilized target substrate. Immediately after, the hydrophobic wrinkled template was placed on the particle suspension without applying external pressure. After drying for approximately 12 h, the wrinkled PDMS template was carefully removed, leaving 1D nanosphere chains on the PDMS target substrate. Numerical calculations. For the electromagnetic simulations, a commercial-grade simulator based on the finite-difference time-domain (FDTD) method was used to perform the calculations (Lumerical Inc., v.8.16, CA). Circularly polarized light was achieved by the superposition of the complex electric and magnetic fields of two separate simulations. The sources of these simulations feature orthogonal linear polarizations at a phase difference of ±90° to obtain left/right circular polarized light, respectively. For the dielectric properties of gold, the data from Johnson and Christy were used. The particle lines were modeled with a particle size of 70 nm, an inter-particle separation (within one chain) ranging from 2 nm to 10 nm. The dipole of the biomolecules was approximated by a chiral medium with a refractive index of 1.38 22 with a rotating axis (90 deg rotation/10 nm) with higher refractive index 1.58 in order to achieve a non-absorbing oriented dipole/medium. Tuning of the chiral medium strength was achieved by a changing of the refractive index of this rotating axis. The simulation space was meshed with 0.5 nm and with 0.1 nm between the particles to capture the rotation of the electric field. The simulation was surrounded by perfect absorbing boundary conditions (perfectly matched layer). To determine the field distributions, the model was simulated at the wavelengths of the corresponding plasmonic (chiral) modes. All simulations reached a convergence of 10 −6 before reaching 500 fs of simulation time. Characterization. Extinction and circular dichroism (CD) spectra were obtained using an RC2 ellipsometer instrument (J. A. WOOLLAM). To in-situ monitor the PCCD under different strains, we mounted the sample on a home-built stretching device and attached it on the ellipsometer to allow the light beam to pass normally through the sample. AFM images were recorded on a Dimension Series Fastscan (Bruker-Nano, Santa Barbara, USA) with the homemade stretching stage in tapping mode with Nanoscope 9.7 using stiff cantilevers TESPA (40 Nm -1 , 300 kHz, Tap300, Budget Sensors, Bulgaria). TEM images were captured using a Zeiss Transmission Electron Microscope Libra120. The SERS measurements were collected in ambient atmosphere with a Reinishaw Invia confocal Raman microscope. The sample, mounted on the stretching device, was illuminated with a 785 nm laser line through a 50× objective, providing a spatial resolution of ca. 1 μm. Laser power at the sample was set to 1 μW with acquisition times of 1 s. The experiment was repeated in ten different positions of the same sample upon stretching. Declarations Data availability All data supporting the findings of this study are available within the paper and its extended data figures. Source data are available with this paper. Acknowledgments Z. Z. acknowlwdges the support from Alexander von Humboldt foundation through a postdoc research fellowship. A. F. and Z. Z. thank the support from Research Council of Lithuania (LMTLT), Culture and Tourism (Germany), and National Science Centre (Poland) fund through a project LaSensA under the M-ERA.NET scheme S-M-ERA.NET-21-2. M. M. acknowledges funding by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation, 453211202). P. T. P. acknowledges the support of elite study programme Macromolecular Science organized by Elitenetzwerk Bayern and University of Bayreuth. N. P.-P., R. A. Á.-P. thank the fundings by the Spanish Ministerio de Ciencia y Tecnoligia (RYC-2015-19107, PID2020-120306RB-I00 and PDC2021-121787-I00), the Generalitat de Cataluña (2017SGR883), the Universitat Rovira i Virgili (2018PFRURV-B2-02), and the Banco Santander (2017EXIT-08). F. L. thanks the Fonds der Chemischen Industrie (FCI) for a Liebig Fellowship. T. A. F. K. acknowledges the financial support by the Volkswagen Foundation through a Freigeist Fellowship. The authors acknowledge Dr. Petr Formanek for the TEM characterization, and Mr. Andreas Janke for the AFM characterization. We thank Mr. Daniel Schletz for the discussion of the electromagnetic simulation. Author contributions Z. Z. and A. F. designed the experiments. Z. Z. and A. M. S. carried out the nanosphere assemblies. Z. Z. and N. S. completed the chirality measurements and the cycling test. P. T. P. and V. G. assisted in the initial chirality measurements. M. M. performed FDTD simulations. N. P.-P., R. A. Á.-P., M. M. and Z. Z. completed the SERS measurements and analysis. Z. Z., A. F., M. M., N. S., T. A. F. K. and F. L. discussed the underlying mechanism of the huge PCCD leap during stretching. Z. Z. and A. F wrote the manuscript. M. M., N. S., T. A. F. K., F. L. and R. A. Á.-P. helped with the writing. All authors edited the manuscript. Competing interest declaration The authors declare no competing interests. References Hazen, R. & Sholl D. Chiral selection on inorganic crystalline surfaces. Nat. Mater. 2 , 367–374 (2003). Valev, V. K., Baumberg, J. J., Sibilia, C. & Verbiest, T. Chirality and chiroptical effects in plasmonic nanostructures: fundamentals, recent progress, and outlook. Adv. Mater. 25 , 2517-2534 (2013). Ma, W., Xu, L., de Moura, A. F., Wu, X., Kuang, H., Xu, C. & N. A. Kotov, Chiral inorganic nanostructures. Chem. Rev. 117 , 8041-8093 (2017). Xu, L., Wang, X., Wang, W., Sun, M., Choi, W. J., Kim, J.-Y., Hao, C., Li, S., Qu, A., Lu, M., Wu, X., Colombari, F. M., Gomes, W. R., Blanco, A. L., de Moura, A. F., Guo, X., Kuang, H., Kotov, N. A. & Xu, C. Enantiomer-dependent immunological response to chiral nanoparticles. Nature 601 , 366–373 (2022). Lee, H.-E., Ahn, H.-Y., Mun, J., Lee, Y. Y., Kim, M., Cho, N. H., Chang, K., Kim, W. S., Rho, J. & Nam, K. T. Amino-acid- and peptide-directed synthesis of chiral plasmonic gold nanoparticles. Nature 556 , 360–365 (2018). Kuzyk, A., Schreiber, R., Fan, Z., Pardatscher, G., Roller, E.-M., Högele, A., Simmel, F. C., Govorov, A. O. & Liedl, T. DNA-based self-assembly of chiral plasmonic nanostructures with tailored optical response. Nature 483 , 311–314 (2012). Lu, J., Xue, Y., Bernardino, K., Zhang, N.-N., Gomes, W. R., Ramesar, N. S., Liu, S., Hu, Z., de Moura, A. F., Kotov, N. A. & Liu, K. Enhanced optical asymmetry in supramolecular chiroplasmonic assemblies with long-range order. Science 371 , 1368-1374 (2021). Gansel, J. K., Thiel, M., Rill, M. S., Decker, M., Bade, K., Saile, V., von Freymann, G., Linden, S. & Wegener, M. Gold helix photonic metamaterial as broadband circular polarizer. Science 325 , 1513-1515 (2009). Guerrero‐Martínez, A., Auguié, B., Alonso‐Gómez, J. L., Džolić, Z., Gómez‐Graña, S., Žinić, M., Cid, M. M. & Liz‐Marzán, L. M. Intense optical activity from three‐dimensional chiral ordering of plasmonic nanoantennas. Angew. Chem. Int. Ed. 50 , 5499-5503 (2011). Hentschel, M., Schäferling, M., Weiss, T., Liu, N. & Giessen, H. Three-dimensional chiral plasmonic oligomers. Nano Lett. 12 , 2542-2547 (2012). Kuzyk, A., Schreiber, R., Zhang, H., Govorov, A. O., Liedl, T. & N. Liu, Reconfigurable 3D plasmonic metamolecules. Nat. Mater. 13 , 862-866 (2014). Probst, P. T., Mayer, M., Gupta, V., Steiner, A. M., Zhou, Z., Auernhammer, G. K., König, T. A. F. & Fery, A. Mechano-tunable chiral metasurfaces via colloidal assembly. Nat. Mater. 20 , 1024–1028 (2021). Zhou, Z., Zhao, Z., Yu, Y., Ai, B., Möhwald, H., Chiechi, R. C., Yang, J. K. W. & G. Zhang, From 1D to 3D: Tunable Sub-10 nm Gaps in Large Area Devices. Adv. Mater. 28 , 2956-2963 (2016). Govorov, A. O., Fan, Z., Hernandez, P., Slocik, J. M. & Naik, R. R. Theory of circular dichroism of nanomaterials comprising chiral molecules and nanocrystals: plasmon enhancement, dipole interactions, and dielectric effects. Nano Lett. 10 , 1374-1382 (2010). Govorov, A. O. Plasmon-induced circular dichroism of a chiral molecule in the vicinity of metal nanocrystals. Application to various geometries. J. Phys. Chem. C 115 , 7914-7923 (2011). Kneer, L. M., Roller, E. M., Besteiro, L. V., Schreiber, R., Govorov, A. O. & Liedl, T. Circular dichroism of chiral molecules in DNA-assembled plasmonic hotspots. ACS nano 12 , 9110-9115 (2018). Hao, C., Xu, L., Sun, M., Ma, W., Kuang, H. & Xu, C. Chirality on Hierarchical Self‐Assembly of Au@AuAg Yolk–Shell Nanorods into Core–Satellite Superstructures for Biosensing in Human Cells. Adv. Funct. Mater. 28 , 1802372 (2018). Cao, Z., Gao, H., Qiu, M., Jin, W., Deng, S., Wong, K. Y. & Lei, D. Chirality Transfer from Sub‐Nanometer Biochemical Molecules to Sub-Micrometer Plasmonic Metastructures: Physiochemical Mechanisms, Biosensing, and Bioimaging Opportunities. Adv. Mater. 32 , 1907151 (2020). Zhang, Q., Hernandez, T., Smith, K. W., Hosseini Jebeli, S. A., Dai, A. X., Warning, L., Guo, H., Chen, D.-H., Dionne, J. A., Landes, C. F. & Link, S. Unraveling the origin of chirality from plasmonic nanoparticle-protein complexes. Science 365 , 1475-1478 (2019). Kim, J. Y. & Kotov, N. A. Origin of chiroptical activity in nanorod assemblies. Science 365 , 1378-1379 (2019). Lan, X., Zhou, X., McCarthy, L. A., Govorov, A. O., Liu, Y. & Link, S. DNA-Enabled Chiral Gold Nanoparticle–Chromophore Hybrid Structure with Resonant Plasmon–Exciton Coupling Gives Unusual and Strong Circular Dichroism. J. Am. Chem. Soc. 141 , 19336-19341(2019). Steiner, A. M., Mayer, M., Seuss, M., Nikolov, S., Harris, K. D., Alexeev, A., Kuttner, C., König, T. A. F. & Fery, A. Macroscopic strain-induced transition from quasi-infinite gold nanoparticle chains to defined plasmonic oligomers. ACS nano 11 , 8871-8880 (2017). Gupta, V., Probst, P. T., Goßler, F. R., Steiner, A. M., Schubert, J., Brasse, Y., König, T. A. F. & Fery, A. Mechanotunable surface lattice resonances in the visible optical range by soft lithography templates and directed self-assembly. ACS Appl. Mater. Interfaces 11 , 28189-28196 (2019). Hanske, C., Tebbe, M., Kuttner, C., Bieber, V., Tsukruk, V. V., Chanana, M., König, T. A. F. & Fery, A. Strongly coupled plasmonic modes on macroscopic areas via template-assisted colloidal self-assembly. Nano Lett. 14 , 6863-6871 (2014). Mayer, M., Potapov, P. L., Pohl, D., Steiner, A. M., Schultz, J., Rellinghaus, B., Lubk, A., König, T. A. F. & Fery, A. Direct observation of plasmon band formation and delocalization in quasi-infinite nanoparticle chains. Nano Lett. 19 , 3854-3862 (2019). Zhu, G., Zhu, X., Fan, Q. & Wan, X. Raman spectra of amino acids and their aqueous solutions. Spectrochim. Acta A Mol. Biomol. Spectrosc. 78 , 1187-1195 (2011). Abdelmoez, W. & Yoshida, H. Production of amino and organic acids from protein using sub-critical water technology. Int. J. Chem. React. 11 , 369-384 (2013). Alvarez-Puebla, R., Liz-Marzán, L. M. & García de Abajo, F. J. Light concentration at the nanometer scale. J. Phys. Chem. Lett. 1 , 2428-2434 (2010). Pazos, E., Garcia-Algar, M., Penas, C., Nazarenus, M., Torruella, A., Pazos-Perez, N., Guerrini, L., Vazquez, M. E., Garcia-Rico, E., Mascarenas, J. L. & Alvarez-Puebla, R. A. Surface-enhanced raman scattering surface selection rules for the proteomic liquid biopsy in real samples: Efficient detection of the oncoprotein c-MYC. J. Am. Chem. Soc. 138 , 14206-14209 (2016). Abdelwahab, M. T., Kalyoncu, E., Onur, T., Baykara, M. Z. & Seker, U. O. S. Genetically-tunable mechanical properties of bacterial functional amyloid nanofibers. Langmuir 33 , 4337-4345 (2017). Moskovits, M. Surface selection rules. J. Chem. Phys. 77 , 4408-4416 (1982). Hanske, C., González-Rubio, G., Hamon, C., Formentín, P., Modin, E., Chuvilin, A., Guerrero-Martínez, A., Marsal, L. F. & Liz-Marzán, L. M. Large-scale plasmonic pyramidal supercrystals via templated self-assembly of monodisperse gold nanospheres. J. Phys. Chem. C 121 , 10899-10906 (2017). Schweikart, A., Fortini, A., Wittemann, A., Schmidt, M. & Fery, A. Nanoparticle assembly by confinement in wrinkles: experiment and simulations. Soft Matter 6 , 5860-5863 (2010). Wang, W., Wu, F., Zhang, Y., Wei, W., Niu, W. & Xu, G. Boosting chiral amplification in plasmon-coupled circular dichroism using discrete silver nanorods as amplifiers. Chem. Commun. 57 , 7390-7393 (2021). Hao, C., Xu, L., Ma, W., Wu, X., Wang, L., Kuang, H. & Xu, C. Unusual circularly polarized photocatalytic activity in nanogapped gold–silver chiroplasmonic nanostructures. Adv. Funct. Mater. 25 , 5816-5822 (2015). Maoz, B. M., van der Weegen, R., Fan, Z., Govorov, A. O., Ellestad, G., Berova, N. & Markovich, G. Plasmonic chiroptical response of silver nanoparticles interacting with chiral supramolecular assemblies. J. Am. Chem. Soc. 134 , 17807-17813 (2012). Slocik, J. M., Govorov, A. O. & Naik, R. R. Plasmonic circular dichroism of peptide-functionalized gold nanoparticles. Nano Lett. 11 , 701-705 (2011). Additional Declarations There is NO Competing Interest. Supplementary Files SupplementaryVideo1.mp4 PEI layer to act as a matrix that transfers strain from the PDMS substrate to the NP chains and subsequently to the BSA molecules between the NPs. SupplementaryVideo2.mp4 MD simulation of stretching induced molecular dipole increase. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1570427","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Letter","associatedPublications":[],"authors":[{"id":426852719,"identity":"29aa003c-bd8d-4fc5-9eab-d0761240fba7","order_by":0,"name":"Ziwei Zhou","email":"","orcid":"","institution":"Leibniz Institute of Polymer Research","correspondingAuthor":false,"prefix":"","firstName":"Ziwei","middleName":"","lastName":"Zhou","suffix":""},{"id":426852720,"identity":"c7252a01-70bf-42a7-882d-312dbda4897d","order_by":1,"name":"Martin Mayer","email":"","orcid":"https://orcid.org/0000-0003-4013-1892","institution":"Leibniz-Institut für Polymerforschung Dresden e.V.","correspondingAuthor":false,"prefix":"","firstName":"Martin","middleName":"","lastName":"Mayer","suffix":""},{"id":426852721,"identity":"43daa7fe-e670-4311-8106-4ba495d07fcb","order_by":2,"name":"Anja Steiner","email":"","orcid":"","institution":"Leibniz Institute of Polymer Research","correspondingAuthor":false,"prefix":"","firstName":"Anja","middleName":"","lastName":"Steiner","suffix":""},{"id":426852722,"identity":"a40cc43f-72d7-4122-aa1d-29609526f265","order_by":3,"name":"Ningwei Sun","email":"","orcid":"","institution":"Technische Universität Dresden","correspondingAuthor":false,"prefix":"","firstName":"Ningwei","middleName":"","lastName":"Sun","suffix":""},{"id":426852723,"identity":"13fc6425-04c8-46af-8d84-6da929f2a0e2","order_by":4,"name":"Patrick Probst","email":"","orcid":"https://orcid.org/0000-0001-7480-9951","institution":"Leibniz-Institut für Polymerforschung Dresden e.V.","correspondingAuthor":false,"prefix":"","firstName":"Patrick","middleName":"","lastName":"Probst","suffix":""},{"id":426852724,"identity":"91dd0bd1-3b9c-4727-92a4-99bf08c3d41c","order_by":5,"name":"Vaibhav Gupta","email":"","orcid":"","institution":"Friedrich-Alexander University Erlangen-Nürnberg","correspondingAuthor":false,"prefix":"","firstName":"Vaibhav","middleName":"","lastName":"Gupta","suffix":""},{"id":426852725,"identity":"2a7f0cab-7122-4707-b772-d627120acba6","order_by":6,"name":"Nicolas Pazos-Perez","email":"","orcid":"","institution":"Universitat Rovira i Virgili","correspondingAuthor":false,"prefix":"","firstName":"Nicolas","middleName":"","lastName":"Pazos-Perez","suffix":""},{"id":426852726,"identity":"fa730d16-2b0e-4f04-9f6a-e97765e2d13c","order_by":7,"name":"Ramon Alvarez-Puebla","email":"","orcid":"https://orcid.org/0000-0003-4770-5756","institution":"Universitat Rovira i Virgili","correspondingAuthor":false,"prefix":"","firstName":"Ramon","middleName":"","lastName":"Alvarez-Puebla","suffix":""},{"id":426852727,"identity":"c269cdb4-c9a1-4dc2-8a10-14d7db12362e","order_by":8,"name":"Franziska Lissel","email":"","orcid":"","institution":"Leibniz Institute of Polymer Research","correspondingAuthor":false,"prefix":"","firstName":"Franziska","middleName":"","lastName":"Lissel","suffix":""},{"id":426852728,"identity":"18015dc5-3687-447e-a869-e2a7a5984427","order_by":9,"name":"Tobias König","email":"","orcid":"https://orcid.org/0000-0002-8852-8752","institution":"Leibniz-Institut für Polymerforschung Dresden e. V.","correspondingAuthor":false,"prefix":"","firstName":"Tobias","middleName":"","lastName":"König","suffix":""},{"id":426852729,"identity":"2aa89fd1-c58b-441b-8e79-d313ef9f26a5","order_by":10,"name":"Andreas Fery","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAtUlEQVRIiWNgGAWjYBAC9gYg8cGAgZ/hQAKDBFFaeA4wMDDOMGCQbCBJCzMPA0la2HufSdsU3JHgO57AeOMDUVp4jptJ5xg8k5A884DZcgYxWuwl0tiAWg7XGdxIYJPmIcoW+Wds0hYGhyXAWv4QpUWCjU2aAaaFGB1Av6QxW/aA/fKw2bKHKC3sxxhv/PgDCrHkgzd+EGUNAwMLMDoOAGnGBiI1AGPyA0TLKBgFo2AUjAIcAACmHzHBHXBQ4QAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0001-6692-3762","institution":"Leibniz Institute of Polymer Research","correspondingAuthor":true,"prefix":"","firstName":"Andreas","middleName":"","lastName":"Fery","suffix":""}],"badges":[],"createdAt":"2022-04-18 22:50:39","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1570427/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1570427/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41563-026-02586-7","type":"published","date":"2026-04-15T04:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":81968798,"identity":"51c37a89-8788-4965-b237-1fc60dc2ee69","added_by":"auto","created_at":"2025-05-05 11:56:21","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":555941,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe stretchable 1D Au@BSA NP array is designed to obtain robust pure PCCD and to establish the role of molecular conformation in PCCD by deforming the substrate.\u003c/strong\u003e \u003cstrong\u003ea,\u003c/strong\u003eSchematic illustration of the 1D Au@BSA nanosphere array. As each BSA molecule located in the plasmonic hotspot between adjacent NPs can contribute to PCCD, the centimeter square assembly array has numerous plasmonic hotspots (visualized by the red clouds between the nanospheres), enhancing the collective PCCD to become a strong signal that can be easily detected through ensemble spectroscopy. \u003cstrong\u003eb,\u003c/strong\u003e To explore the influence of molecular conformation on PCCD, the soft PDMS substrate is stretched along the interparticle-axis direction, gradually enlarging the gaps between the nanospheres in each chain (\u003cstrong\u003ec\u003c/strong\u003e-\u003cstrong\u003ee\u003c/strong\u003e, AFM images). This causes the BSA molecules in the hotspots to go from a random oriented state to an aligned state along the stretching direction and allows us to monitor the BSA reconformation in real-time. \u003cstrong\u003ef,\u003c/strong\u003e The oligomer length distributions of the original state and the 40% strain state, showing the splitting of the Au@BSA nanosphere chains during stretching.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-1570427/v1/e4251095d06797499c624c6c.png"},{"id":81967447,"identity":"b46f1fea-55a4-42f0-a8c8-e050112750ae","added_by":"auto","created_at":"2025-05-05 11:40:21","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":207303,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eStrain-induced PCCD enhancement of the 1D Au@BSA nanosphere array upon continuous substrate stretching and superior cycling stability. a, \u003c/strong\u003eCollective PCCD spectra of the 1D Au@BSA nanosphere assembly array with the external strain increasing from 0% to 55%. The black dotted line depicts the CD spectrum of a PEG@Au nanosphere assembly, showing no CD signal due to the achirality of the PEG molecules. \u003cstrong\u003eb,\u003c/strong\u003e The red symbols and purple line plot the changes of the peak PCCD values during the stretching-releasing process. This increasing trend fits a half-linear curve (dotted line). \u003cstrong\u003ec,\u003c/strong\u003e Collective PCCD spectra of 15 stretching-releasing cycles, showing the outstanding reproducibility of the response. The insets show the optical photos of the 1D chiral assembly array in stretching and releasing states. \u003cstrong\u003ed,\u003c/strong\u003e Records of the peak CD values during the cycling test over 100 cycles and the self-healing behavior of the CD value after immersing into water overnight.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-1570427/v1/7b1dfa943927e7d9622d4955.png"},{"id":81967450,"identity":"1b367619-5ec6-42c9-9cc8-6a431964970c","added_by":"auto","created_at":"2025-05-05 11:40:22","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":617380,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eContinuous changes on the plasmonic performance of the 1D Au@protein nanosphere assembly during the strain-induced PCCD leap. a, \u003c/strong\u003eExtinction spectra of the BSA@Au nanosphere chain assembly on a PDMS substrate with increasing strain from 0% to 55% for incident LCP and RCP light. The green dashed lines label the transversal plasmonic mode and the yellow dotted lines indicate the longitudinal plasmonic mode. The grey lines represent the corresponding CD spectra for a comparison. \u003cstrong\u003eb,\u003c/strong\u003e SERS intensities of the 1D assembly during stretching process. A 785 nm laser line was used with a power of 1 μW at the sample and acquisition time of 1 s. \u003cstrong\u003ec,\u003c/strong\u003e Intensity of the SERS spectra as a function of the stretching percentage. Values are an average of over ten different spots collected for each sample for ring C-C stretching of Phe at 1080 cm\u003csup\u003e-1\u003c/sup\u003e.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-1570427/v1/8b7c35ed67f0511c57a78365.png"},{"id":81967451,"identity":"78801212-e710-43be-9f97-1a8d397abf62","added_by":"auto","created_at":"2025-05-05 11:40:22","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":286470,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eEffects of the molecular conformations on PCCD of the 1D Au@protein nanosphere assembly during stretching. a,\u003c/strong\u003e Visualized BSA conformational change upon strain, where the soft random coils are pulled and the rigid α-helices become more aligned along the stretching direction. \u003cstrong\u003eb,\u003c/strong\u003eSimulated CD spectra of 1D BSA@nanosphere assembly with the chiral molecule in perpendicular (black line) and parallel (red line) orientation to the interparticle axis. \u003cstrong\u003ec,\u003c/strong\u003e Simulated extinction spectra of 1D BSA@nanosphere assembly with increasing dipole strength. \u003cstrong\u003ed, e,\u003c/strong\u003e Simulated electric field and surface charge of 1D nanosphere assembly.\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-1570427/v1/a9394a9ed75e0c7819d27a44.png"},{"id":107045291,"identity":"172703d6-e28c-41d5-9471-cea41fadb50f","added_by":"auto","created_at":"2026-04-16 07:17:08","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2541890,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1570427/v1/6f3293b7-91c8-4e39-a29d-d3e9def425fd.pdf"},{"id":81967453,"identity":"84e775a6-4286-4d69-ac6e-6e852cc22cad","added_by":"auto","created_at":"2025-05-05 11:40:22","extension":"mp4","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":38795041,"visible":true,"origin":"","legend":"PEI layer to act as a matrix that transfers strain from the PDMS substrate to the NP chains and subsequently to the BSA molecules between the NPs.","description":"","filename":"SupplementaryVideo1.mp4","url":"https://assets-eu.researchsquare.com/files/rs-1570427/v1/f442056964c42d69a21ec907.mp4"},{"id":81967446,"identity":"852570fc-9259-48fa-a181-837274d66d90","added_by":"auto","created_at":"2025-05-05 11:40:21","extension":"mp4","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":175437,"visible":true,"origin":"","legend":"MD simulation of stretching induced molecular dipole increase.","description":"","filename":"SupplementaryVideo2.mp4","url":"https://assets-eu.researchsquare.com/files/rs-1570427/v1/6f72926a666c70d7726810ac.mp4"},{"id":81968032,"identity":"657bb073-7800-4e12-b85e-3aa8d6121248","added_by":"auto","created_at":"2025-05-05 11:48:21","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":1267291,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"ExtendedData.docx","url":"https://assets-eu.researchsquare.com/files/rs-1570427/v1/4fadb9f85923c6e0977183f0.docx"},{"id":81967452,"identity":"95787139-fba3-44d6-81e5-fd7b67a35624","added_by":"auto","created_at":"2025-05-05 11:40:22","extension":"docx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":5769200,"visible":true,"origin":"","legend":"\u003cp\u003eSupplymentary Information\u003c/p\u003e","description":"","filename":"SupplementaryInformation.docx","url":"https://assets-eu.researchsquare.com/files/rs-1570427/v1/8234e9c0f379e4cfbd81020a.docx"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"Highly efficient and switchable chirality transfer between protein and achiral plasmonic assemblies","fulltext":[{"header":"Introduction","content":"\u003cp\u003eNature creates chiral biomolecules to support corresponding biological processes\u003csup\u003e1\u003c/sup\u003e. Various kinds of biomolecules occupy a big family in molecular chirality. While at nanoscale, when chirality meets plasmonic nanostructures, intense circular dichroism (CD) in the visible-near-infrared range is generated, which is stronger than the (bio)molecular CD that are usually located in the ultraviolet (UV) range. Harnessing this, chiral plasmonics gives access to powerful polarization control and enantiomer sensing/catalysis\u003csup\u003e2-5\u003c/sup\u003e. Nowadays, helical\u003csup\u003e6-9\u003c/sup\u003e and scissor-like\u003csup\u003e10-13\u003c/sup\u003e chiral nanostructures can be realized through DNA origami or lithographic methods. Nevertheless, the fabrication of artificial chiral nanostructures is significantly more onerous. That is why recently researchers have endeavored more and more in transferring the effortless biomolecular chirality to plasmonic nanostructures\u003csup\u003e5-7\u003c/sup\u003e. In the pioneering studies with this goal, biomolecules act as a template to direct the plasmonic nanostructure into a chiral shape, where the chirality transfer is irreversible. Thus, the question arises: is it possible to transfer (bio) molecular chirality efficiently and reversibly to plasmonic nanostructures? It remains one of the holy grails in light matter interaction, as it could open a dynamic new world of plasmonic chirality independent from the tedious fabrication of sophisticated nanostructures.\u003c/p\u003e\n\u003cp\u003ePlasmon-coupled CD (PCCD) provides the possibility of the reversible chirality transfer, as it transfers the molecular chirality electrostatically onto the achiral nanostructures without breaking of symmetry\u003csup\u003e14-21\u003c/sup\u003e. Put differently, the dipole/multipole of a chiral molecule can electrostatically induce a chiral response on the achiral plasmonics, where the biomolecule is an interaction host rather than a chiral template. However, PCCD is usually too weak and is inversely proportional to the distance between chiral molecule and plasmonic nanostructure\u003csup\u003e14,15\u003c/sup\u003e. Accordingly, up to date people have put most efforts in accommodating the chiral molecules into various kinds of narrow nanogaps\u003csup\u003e16-21\u003c/sup\u003e, which provide plasmonic hotspots to enhance PCCD while ensuring molecules and nanostructures in close range. Even so, the state-of-the-art of PCCD is still far from an efficient chirality transfer, which is much lower than the structurally transferred CD. Other factors should also be considered besides plasmonic hotspots. For example, similar efforts regarding the (bio)molecular side are much more limited\u003csup\u003e18\u003c/sup\u003e, mainly because most molecule-nanostructure complexes are static, which makes it difficult to probe the molecular component and monitor the induced changes in PCCD. However, as biomolecules are the chiral chromophores in PCCD, understanding the molecular side and optimizing it may lead to a leverage effect on signal amplification. The prerequisite for investigating the molecular aspects\u0026mdash;to better understand the transfer mechanism and efficiently transfer more intense CD from biomolecules\u0026mdash;is the realization of smarter nanostructures that allow researchers to easily deform and probe the molecules in real time.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConstruction of stretchable 1D linear nanoparticle-protein complex array stipulating pure PCCD\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo address this, we designed a structurally non-chiral one-dimensional (1D) linear chain array of Au nanospheres conjugated to bovine serum albumin (BSA) with an average diameter of 70.6 nm (Extended Data Fig. S1) based on a template-assisted colloidal self-assembly strategy\u003csup\u003e22-25\u003c/sup\u003e. These single nanospheres carrying BSA imparted negligible PCCD that can hardly be detected\u003csup\u003e11\u003c/sup\u003e due to the lack of plasmonic hotspots and structural asymmetry (Extended Data Fig. S2). Arranging such single-crystalline spherical building blocks in a 1D linear assembly enables us to completely exclude structural chirality, thus rendering the BSA molecules as the sole origin of chirality (Fig. 1a and Extended Data Fig. S2). At the same time, the high-density plasmonic hotspots in the assembly promote the collective PCCD to an amount that can be detected by common ensemble spectroscopy (~ 50 mdeg, grey line in Fig. 2a), which owns the opposite handedness to the molecular chirality of BSA in the UV region (see the full CD spectrum in Extended Data Fig. S3). While, a 1D linear assembly of Au nanospheres conjugated to polyethylene glycol (PEG) showed no CD signal due to the achirality of the PEG molecules, thus confirming the achirality of the 1D chain nanostructure (Extended Data Fig. S2). Furthermore, as a thin adhesive layer of polyethylenimine (PEI) cast onto polydimethylsiloxane (PDMS) substrate (in which the nanospheres are partially embedded for ~20 nm, 29%)\u003csup\u003e22\u003c/sup\u003e acts as a matrix to transfer the strain from the substrate to the nanospheres and thus also to the proteins bridging the nanospheres. Hence, stretching the soft elastomeric PDMS substrate gradually (Fig. 1b) allows the stretching of the proteins bridging the nanospheres. With increasing strain along the nanosphere chain direction, atomic force microscopy (AFM) images indicated that the nanospheres are gradually separated (Fig. 1c-e and Extended Data Fig. S4). Simultaneously, the bridged tangled proteins are re-conformed from a random oriented state to an aligned state and later even to a stretched state, providing us with a model system that allows to access a range of chiral molecular conformations, and to systematically investigate the underlying mechanism of chirality transfer from biomolecules to plasmonic fields.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAnomaly PCCD leap during stretching and its superb reversibility\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWhen the external strain is gradually increased from 0% to 55%, the nanosphere chain split into oligomers, within which the interparticle nanogaps enlarge gradually (Fig. 1c-e and Extended Data Fig. S4). In the state-of-the-art theory, the contribution PCCD should rapidly decrease because the nanosphere-molecule center-to-center distance increases and the plasmonic hotspots weakens simultaneously. While by contraries, the collective PCCD increases drastically by a factor of up to 22 (Fig. 2a-b). The observed collective PCCD intensity reached up to 1.36 deg at a wavelength of ~700 nm with a g-factor of 0.2 (Fig. 2a and Extended Data Fig. S5). Both the obtained intensity and g-factor are between 10 and 1000 times greater than those previously observed PCCD (Extended Data Table S1), and the achieved CD strength and g-factor are comparable to or even higher than conventional structural CD. Therefore, the stereotype of low efficiency of PCCD has been completely broken.\u003c/p\u003e\n\u003cp\u003ePCCD is highly sensitive to the external strain along the nanosphere chain direction. The increasing tendency of the strain-induced PCCD leap shows a non-linear trend: After an initial phase with a linear increase, the gradient is decreasing at about 25%, until a plateau is reached at about 55% strain as plotted in Fig. 2b. Upon release, the system returns to the initial low PCCD value. The stretching process is continuous and highly stable, allowing control of the PCCD using strain as an external stimulus with an outstanding cycling stability: Even after 100 cycles from 0% to 50% strain (Fig. 2d), the high modulation contrast is retained only with a slight drop of CD intensity (~ 4%). But when the assembly was immersed into water overnight, the CD intensity self-healed to original due to the re-intertwined protein segments. Most chiral nanostructures are 3D or quasi-3D, which means that chiral tuning also requires a structural deformation in multiple dimension\u003csup\u003e10-13\u003c/sup\u003e. In contrast, in our 1D assembly the deformation in just one dimension is sufficient to powerfully tune the chirality of the whole plasmonic structure. This reduction of dimensionality enables a much simpler and more robust chirality switching.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMonitoring of the plasmonic properties of the nanoparticle-protein complexes during stretching\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs PCCD results from the interaction between plasmonic modes and molecular chirality\u003csup\u003e14,15\u003c/sup\u003e, both contribute simultaneously to PCCD as a whole. So far, research efforts have focused on the plasmonic side, showing that stronger hotspots generate stronger PCCD\u003csup\u003e14-21\u003c/sup\u003e. But our results above validated that something beyond the plasmonic side plays a leverage effect on PCCD. To make it clearer, we first examined the changes of the plasmonic properties of the 1D chiral array during the stretching process (Fig. 3a). The 1D linear NP chain array has two plasmonic peaks in the extinction spectra (marked by the green and orange dotted lines, Fig. 3a), representing the transversal and longitudinal plasmonic modes respectively. From the extinction spectra during stretching, we can see that the difference in extinction between left-handed circularly polarized (LCP) light and right-handed circularly polarized (RCP) light mainly originates from the longitudinal mode\u003csup\u003e19\u003c/sup\u003e, indicating that mainly the BSA molecules located between the nanospheres contribute to the collective PCCD. While the peak position of the transversally dominated mode stays nearly constant, together with an increasing extinction intensity. As for the longitudinally dominated mode, it experiences a slight blue-shift, implying the splitting of the nanosphere chain and the weakening of the plasmonic hotspots upon strain. The sharpening of both plasmonic peaks during stretching indicates the more centralized oligomer length distributions during stretching (Fig. 1f).\u003c/p\u003e\n\u003cp\u003eThe decrease of the electric field enhancement in the hotspots was further traced by surface-enhanced Raman scattering (SERS) measurements of the 1D assembly during stretching, as shown in Fig. 3b, c. The sample as it is, without stretching, shows typical contributions from phenylamine (Phe) (1004, 1030 and 1080 cm\u003csup\u003e-1\u003c/sup\u003e) with weaker signals at 914, 955, 1100 and 1168 cm\u003csup\u003e-1\u003c/sup\u003e, due to lysine (Lys)\u003csup\u003e26\u003c/sup\u003e. The Phe contribution is expected due to both its large percentage in the composition of BSA and its large Raman cross-section as compared with the rest of the amino acids\u003csup\u003e27\u003c/sup\u003e. In the case of Lys, the weak bands observed are consistent with its large concentration in BSA. Notably, upon stretching two phenomena occur. First, some of the SERS signals, those related to Lys disappear; and second, while in the case of Phe the bands continue to be present, their absolute intensity decreases with stretching, with an additional change in their relative intensity. Simultaneously, the disappearance of the signal of Lys and the exponential decrease of the signal of Phe upon stretching can be explained by the strain-induced enlargement of the intergap size in the nanosphere chain assembly (Fig. 1d). As this gap enlarges, the energy of the electromagnetic hotspot formed by the plasmon intercoupling between two neighbor particles exponentially decrease with the subsequent decrease in the SERS intensity (Fig. 3c)\u003csup\u003e28\u003c/sup\u003e. On the other hand, the changes of the relative intensity in the Phe signals clearly point towards to Phe reorientation as the protein is stretched\u003csup\u003e29,30\u003c/sup\u003e, as a clear demonstration of the surface selection rules\u003csup\u003e31\u003c/sup\u003e. Therefore, concerning the plasmonic side, the hotspots were indeed weakened during stretching. However counterintuitively, we observed a strong PCCD increase, indicating that strain-induced reformation from the molecular side plays a much more important role than the plasmonic hotspots.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHow a biomolecule reversibly turns an achiral nanoparticle strongly chiral\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIt is very interesting that the chiral molecules in the assembly only represent a small fraction of the ensemble (theoretically only few BSA molecules could fit in a gap according to the gap volume)\u003csup\u003e19\u003c/sup\u003e, but upon stretching have such a large effect on the PCCD. To decode this, we have to zoom in on the structural arrangement: When the Au@BSA nanospheres are assembled in the PDMS wrinkles and drying, the nanospheres get close and the segments of adjacent BSA shells tangle with each other due to the capillary force (Extended Data Fig. S1). After drying, the BSA molecules in the gaps of nanosphere chains shrink and present a random globular state (Fig. 4a, left panel). As the protein structure is abundant in both rigid \u0026alpha;-helices and flexible random coils, BSA can also be stretched upon strain by pulling the random coils, while the rigid \u0026alpha;-helices which mainly feature the dipoles, become more aligned along the direction of strain (Fig. 4a, right panel), increasing the collective dipoles of BSA. Accordingly, we infer that the strain-induced stretching of the BSA molecules is intimately connected to the observed PCCD leap.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis raises a fundamental question: Why would the stretching of a chiral molecule sharply enhance the PCCD? We know PCCD is based on the electrostatic interaction between a chiral molecular dipole and plasmonic bands; a stronger molecular dipole will thereby induce a more chirally polarized plasmons\u003csup\u003e14,15\u003c/sup\u003e. Additionally, for a molecular dipole, the parallel alignment to the interparticle axis is favored to PCCD compared with the perpendicular or even random orientation, since the CD signal proportionally scales to the dipole moments along the interparticle axis\u003csup\u003e14,15\u003c/sup\u003e. During the stretching process, the BSA molecules bridging the nanospheres are tightly stretched and elongated, resulting in a rising parallel molecular conformation with regard to the particle axis (Fig. 4a). Furthermore, the stretching of a chiral molecule may result in an increase of the effective dipole length, which will also increase the collective molecular dipole of a chiral molecule (Fig. 4a). Enhanced molecular dipole by stretching thus results in the ultrastrong chiral pattern on the achiral nanospheres and achieve the PCCD leap.\u003c/p\u003e\n\u003cp\u003eElectromagnetic simulations were performed to confirm the enhanced PCCD effect. Rotation of the simulated dipole of a chiral molecule by 90\u0026deg; results in a drastic drop of the differential extinction (Fig. 4b), exhibiting that a head-to-head orientation of molecular dipole is preferred in PCCD. Furthermore, holding on this preferred orientation, simulations show that the effect can be even more pronounced if the particle spacing remains unchanged and only the molecular dipole is strengthened (Fig. 4c). The simulations of electric field (Fig. 4d) of the nanosphere assembly present the plasmonic hotspots along the chain direction. While the simulation of surface charge distribution (Fig. 4e) shows the electrostatic interaction in the gaps for PCCD between chiral molecules and plasmons. The simulation can well match our experimental results and help to confirm the huge impact of molecular conformation on PCCD enhancement.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSummary and outlook\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOur stretching-molecule strategy realized the efficient and reversible chirality transfer between molecular scale and nanoscale for the first time, overcoming the size-mismatching of the two interacting components and the intense dependence of strong plasmonic hotspots. It will promote convenient and ultrastrong plasmonic chirality consisting of biomolecules and arbitrary achiral nanostructures, enabling the directly borrowed plasmonic chirality from natural molecules. Notably, due to the unique electrostatic interaction between biomolecules and achiral nanoparticles, this chirality transfer can be dynamically reversed for over 100 times, providing guidance for the design of smart chiroplasmonic nanocomposites for biosensing and optoelectronics. The stretching-molecule strategy can also be achieved by many other stimuli other than the mechanical strain in this work, for example solvents, pH, light, electric and temperature that can increase the dipole of the chiral molecule. Therefore, our stretching-molecule strategy is versatile for tailoring various smart CD devices without sophisticated 3D nanofabrication.\u003c/p\u003e\n\u003cp\u003eWe anticipate our assay to be a starting point for showing the giant protein power when interacting with plasmonic nanostructures. Only a stretch of protein will stir the plasmons tremendously. This could also in turn allow sensing mechanical properties of proteins (e.g., conformation and unfolding energetics) under strain through the robust plasmonic CD at a level of few or even single molecules. Biomolecules are an important part of nature and the more we know about them and the underlying chirality transfer mechanism, the more we can communicate with nature.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e\u003cstrong\u003eChemicals.\u003c/strong\u003e Hydrogen tetrachloroaurate (HAuCl\u003csub\u003e4\u003c/sub\u003e, \u0026gt;99.9%), sodium borohydride (NaBH\u003csub\u003e4\u003c/sub\u003e, 99%), L-ascorbic acid (AA, C\u003csub\u003e6\u003c/sub\u003eH\u003csub\u003e8\u003c/sub\u003eO\u003csub\u003e6\u003c/sub\u003e, \u0026gt;99%), bovine serum albumin (BSA, 98%), hexadecyltrimethylammonium chloride (CtaC, 25 wt % in water), and polyethylenimine (PEI, Mw 2 kg/mol, linear, 50 wt% in water) were purchased from Sigma-Aldrich. Hexadecyltrimethylammonium bromide (CtaB, 99%) was supplied by Merck KGaA. Sodium hydroxide (NaOH, 1 M) solutions and trisodium citrate (Na\u003csub\u003e3\u003c/sub\u003eC\u003csub\u003e6\u003c/sub\u003eH\u003csub\u003e5\u003c/sub\u003eO\u003csub\u003e7\u003c/sub\u003e, \u0026gt;99%) were received from Grussing. Sylgard 184 PDMS elastomer kits were purchased from Dow Corning. All chemicals were used without further purification. High-purity deionized water (18.2 M\u0026Omega; cm\u003csup\u003e-1\u003c/sup\u003e) was used in all aqueous preparations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSynthesis and functionalization of single-crystalline nanospheres.\u003c/strong\u003e The Au nanospheres were synthesized, as reported previously, followed by a ligand exchange process to a BSA/PEG coating\u003csup\u003e22\u003c/sup\u003e. First, 2 nm Au seeds were prepared through reduction of HAuCl\u003csub\u003e4\u003c/sub\u003e using NaBH\u003csub\u003e4\u003c/sub\u003e with CtaB as stabilizer. Further the Au seeds were twice grown in solution (containing HAuCl\u003csub\u003e4\u003c/sub\u003e, ascorbic acid and CtaC) to a final diameter of ~70.6\u0026plusmn;1.2 nm. Additionally, in the last growth step, a syringe pump system was invoked to ensure kinetic control of Au growth. The final product was collected by centrifugation and washed twice with a 2 mM CtaC solution. Finally, the CtaC stabilizers could be readily exchanged with either chiral ligands such as BSA\u003csup\u003e22\u003c/sup\u003e or achiral ligand such as PEG\u003csup\u003e32\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLarge scale 1D nanosphere assembly.\u003c/strong\u003e The wrinkled templates with a wavelength and amplitude of ~370 nm and ~35 nm, respectively, were obtained according to the previously published procedure. PDMS was prepared by casting the mixed cross-linker/prepolymer mixture (1:5, Sylgard 184, Dow Corning) in a leveled polystyrene dish and then by degassing in a vacuum. The PDMS mixture was cross-linked at 80 \u0026deg;C with a final thickness of ~2 mm. The cured PDMS was cut into 1 \u0026times; 4.5 cm\u003csup\u003e2\u003c/sup\u003e strips. To achieve PDMS wrinkles, these strips were fixed in a home-built stretching device and elongated by 40%. The elongated PDMS strips were then O\u003csub\u003e2\u003c/sub\u003e-plasma-treated (Flecto 10, Plasma Technology) for 120 s (100 W, 0.3 mbar O\u003csub\u003e2\u003c/sub\u003e). The plasma-treated PDMS strip was then cooled to RT and slowly released. The obtained PDMS wrinkling was cut into 1 \u0026times; 1 cm\u003csup\u003e2\u003c/sup\u003e stripes as templates to guide the nanospheres into closely packed 1D linear assemblies by spin-coating as previously reported. Three microliters of Au nanosphere suspension ([Au\u003csup\u003e0\u003c/sup\u003e] = 12 mg/mL, pH 11) was spread onto the PDMS wrinkled template, followed by a two-stage spin-coating process (30 s at 1500 rpm, and 30 s at 4000 rpm, photoresist spinner, Headway Research Inc.). After drying, the assembly took on a rose/grey color with angle-dependent anisotropy.\u003c/p\u003e\n\u003cp\u003eThe 1D nanosphere assemblies trapped inside the PDMS wrinkles were then wet-transferred onto a flat PDMS substrate for better optical performance. The target PDMS with a cross-linker/prepolymer mixing ratio of 1:15 was cured as above. Subsequently the target PDMS substrate was incubated with a 10 mg/mL PEI solution for 3h to apply an adhesion layer on top, promoting complete transfer of the nanosphere assemblies. For the wet transfer, a droplet of water (pH 9) was placed on the center of the target PDMS substrate. With a pressure of 100 kPa the nanosphere-filled PDMS stamp was pressed onto the target PDMS. After drying and detaching, the 1D nanosphere chains were transferred to the flat PDMS substrate.\u003c/p\u003e\n\u003cp\u003eIn contrast, PEG-coated nanoparticles were directly assembled on PDMS stripes by confinement assembly technique\u003csup\u003e33\u003c/sup\u003e. For this the target PDMS was prepared and hydrophilized as described above. Four microliters of the PEG coated nanoparticles were placed on the hydrophilized target substrate. Immediately after, the hydrophobic wrinkled template was placed on the particle suspension without applying external pressure. After drying for approximately 12 h, the wrinkled PDMS template was carefully removed, leaving 1D nanosphere chains on the PDMS target substrate.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNumerical calculations.\u003c/strong\u003e For the electromagnetic simulations, a commercial-grade simulator based on the finite-difference time-domain (FDTD) method was used to perform the calculations (Lumerical Inc., v.8.16, CA). Circularly polarized light was achieved by the superposition of the complex electric and magnetic fields of two separate simulations. The sources of these simulations feature orthogonal linear polarizations at a phase difference of \u0026plusmn;90\u0026deg; to obtain left/right circular polarized light, respectively. For the dielectric properties of gold, the data from Johnson and Christy were used. The particle lines were modeled with a particle size of 70\u0026thinsp;nm, an inter-particle separation (within one chain) ranging from 2\u0026thinsp;nm to 10 nm. The dipole of the biomolecules was approximated by a chiral medium with a refractive index of 1.38\u003csup\u003e22\u003c/sup\u003e with a rotating axis (90 deg rotation/10 nm) with higher refractive index 1.58 in order to achieve a non-absorbing oriented dipole/medium. Tuning of the chiral medium strength was achieved by a changing of the refractive index of this rotating axis. The simulation space was meshed with 0.5\u0026thinsp;nm and with 0.1 nm between the particles to capture the rotation of the electric field. The simulation was surrounded by perfect absorbing boundary conditions (perfectly matched layer). To determine the field distributions, the model was simulated at the wavelengths of the corresponding plasmonic (chiral) modes. All simulations reached a convergence of 10\u003csup\u003e\u0026minus;6\u003c/sup\u003e before reaching 500\u0026thinsp;fs of simulation time.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCharacterization.\u003c/strong\u003e Extinction and circular dichroism (CD) spectra were obtained using an RC2 ellipsometer instrument (J. A. WOOLLAM). To in-situ monitor the PCCD under different strains, we mounted the sample on a home-built stretching device and attached it on the ellipsometer to allow the light beam to pass normally through the sample. AFM images were recorded on a Dimension Series Fastscan (Bruker-Nano, Santa Barbara, USA) with the homemade stretching stage in tapping mode with Nanoscope 9.7 using stiff cantilevers TESPA (40 Nm\u003csup\u003e-1\u003c/sup\u003e, 300 kHz, Tap300, Budget Sensors, Bulgaria). TEM images were captured using a Zeiss Transmission Electron Microscope Libra120. The SERS measurements were collected in ambient atmosphere with a Reinishaw Invia confocal Raman microscope. The sample, mounted on the stretching device, was illuminated with a 785 nm laser line through a 50\u0026times; objective, providing a spatial resolution of ca. 1 \u0026mu;m. Laser power at the sample was set to 1 \u0026mu;W with acquisition times of 1 s. The experiment was repeated in ten different positions of the same sample upon stretching.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data supporting the findings of this study are available within the paper and its extended data figures. Source data are available with this paper.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eZ. Z. acknowlwdges the support from Alexander von Humboldt foundation through a postdoc research fellowship. A. F. and Z. Z. thank the support from Research Council of Lithuania (LMTLT), Culture and Tourism (Germany), and National Science Centre (Poland) fund through a project LaSensA under the M-ERA.NET scheme S-M-ERA.NET-21-2. M. M. acknowledges funding by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation, 453211202). P. T. P. acknowledges the support of elite study programme Macromolecular Science organized by Elitenetzwerk Bayern and University of Bayreuth. N. P.-P., R. A. \u0026Aacute;.-P. thank the fundings by the Spanish Ministerio de Ciencia y Tecnoligia (RYC-2015-19107, PID2020-120306RB-I00 and PDC2021-121787-I00), the Generalitat de Cataluña (2017SGR883), the Universitat Rovira i Virgili (2018PFRURV-B2-02), and the Banco Santander (2017EXIT-08). F. L. thanks the Fonds der Chemischen Industrie (FCI) for a Liebig Fellowship. T. A. F. K. acknowledges the financial support by the Volkswagen Foundation through a Freigeist Fellowship. The authors acknowledge Dr. Petr Formanek for the TEM characterization, and Mr. Andreas Janke for the AFM characterization. We thank Mr. Daniel Schletz for the discussion of the electromagnetic simulation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eZ. Z. and A. F. designed the experiments. Z. Z. and A. M. S. carried out the nanosphere assemblies. Z. Z. and N. S. completed the chirality measurements and the cycling test. P. T. P. and V. G. assisted in the initial chirality measurements. M. M. performed FDTD simulations. N. P.-P., R. A. \u0026Aacute;.-P., M. M. and Z. Z. completed the SERS measurements and analysis. Z. Z., A. F., M. M., N. S., T. A. F. K. and F. L. discussed the underlying mechanism of the huge PCCD leap during stretching. Z. Z. and A. F wrote the manuscript. M. M., N. S., T. A. F. K., F. L. and R. A. \u0026Aacute;.-P. helped with the writing. All authors edited the manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interest declaration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eHazen, R. \u0026amp; Sholl D. Chiral selection on inorganic crystalline surfaces. \u003cem\u003eNat. Mater.\u003c/em\u003e \u003cstrong\u003e2\u003c/strong\u003e, 367\u0026ndash;374 (2003).\u003c/li\u003e\n \u003cli\u003eValev, V. K., Baumberg, J. J., Sibilia, C. \u0026amp; Verbiest, T. Chirality and chiroptical effects in plasmonic nanostructures: fundamentals, recent progress, and outlook. \u003cem\u003eAdv. Mater.\u003c/em\u003e \u003cstrong\u003e25\u003c/strong\u003e, 2517-2534 (2013).\u003c/li\u003e\n \u003cli\u003eMa, W., Xu, L., de Moura, A. F., Wu, X., Kuang, H., Xu, C. \u0026amp; N. A. Kotov, Chiral inorganic nanostructures. \u003cem\u003eChem. Rev.\u003c/em\u003e\u003cstrong\u003e117\u003c/strong\u003e, 8041-8093 (2017).\u003c/li\u003e\n \u003cli\u003eXu, L., Wang, X., Wang, W., Sun, M., Choi, W. J., Kim, J.-Y., Hao, C., Li, S., Qu, A., Lu, M., Wu, X., Colombari, F. M., Gomes, W. R., Blanco, A. L., de Moura, A. F., Guo, X., Kuang, H., Kotov, N. A. \u0026amp; Xu, C. Enantiomer-dependent immunological response to chiral nanoparticles. \u003cem\u003eNature\u003c/em\u003e \u003cstrong\u003e601\u003c/strong\u003e, 366\u0026ndash;373 (2022).\u003c/li\u003e\n \u003cli\u003eLee, H.-E., Ahn, H.-Y., Mun, J., Lee, Y. Y., Kim, M., Cho, N. H., Chang, K., Kim, W. S., Rho, J. \u0026amp; Nam, K. T. Amino-acid- and peptide-directed synthesis of chiral plasmonic gold nanoparticles. \u003cem\u003eNature\u003c/em\u003e \u003cstrong\u003e556\u003c/strong\u003e, 360\u0026ndash;365 (2018).\u003c/li\u003e\n \u003cli\u003eKuzyk, A., Schreiber, R., Fan, Z., Pardatscher, G., Roller, E.-M., H\u0026ouml;gele, A., Simmel, F. C., Govorov, A. O. \u0026amp; Liedl, T. DNA-based self-assembly of chiral plasmonic nanostructures with tailored optical response. \u003cem\u003eNature\u003c/em\u003e \u003cstrong\u003e483\u003c/strong\u003e, 311\u0026ndash;314 (2012).\u003c/li\u003e\n \u003cli\u003eLu, J., Xue, Y., Bernardino, K., Zhang, N.-N., Gomes, W. R., Ramesar, N. S., Liu, S., Hu, Z., de Moura, A. F., Kotov, N. A. \u0026amp; Liu, K. Enhanced optical asymmetry in supramolecular chiroplasmonic assemblies with long-range order. \u003cem\u003eScience\u003c/em\u003e \u003cstrong\u003e371\u003c/strong\u003e, 1368-1374 (2021).\u003c/li\u003e\n \u003cli\u003eGansel, J. K., Thiel, M., Rill, M. S., Decker, M., Bade, K., Saile, V., von Freymann, G., Linden, S. \u0026amp; Wegener, M. Gold helix photonic metamaterial as broadband circular polarizer. \u003cem\u003eScience\u003c/em\u003e \u003cstrong\u003e325\u003c/strong\u003e, 1513-1515 (2009).\u003c/li\u003e\n \u003cli\u003eGuerrero‐Mart\u0026iacute;nez, A., Augui\u0026eacute;, B., Alonso‐G\u0026oacute;mez, J. L., Džolić, Z., G\u0026oacute;mez‐Gra\u0026ntilde;a, S., Žinić, M., Cid, M. M. \u0026amp; Liz‐Marz\u0026aacute;n, L. M. Intense optical activity from three‐dimensional chiral ordering of plasmonic nanoantennas. \u003cem\u003eAngew. Chem. Int. Ed.\u003c/em\u003e \u003cstrong\u003e50\u003c/strong\u003e, 5499-5503 (2011).\u003c/li\u003e\n \u003cli\u003eHentschel, M., Schäferling, M., Weiss, T., Liu, N. \u0026amp; Giessen, H. Three-dimensional chiral plasmonic oligomers. \u003cem\u003eNano Lett.\u003c/em\u003e \u003cstrong\u003e12\u003c/strong\u003e, 2542-2547 (2012).\u003c/li\u003e\n \u003cli\u003eKuzyk, A., Schreiber, R., Zhang, H., Govorov, A. O., Liedl, T. \u0026amp; N. Liu, Reconfigurable 3D plasmonic metamolecules. \u003cem\u003eNat. Mater.\u003c/em\u003e \u003cstrong\u003e13\u003c/strong\u003e, 862-866 (2014).\u003c/li\u003e\n \u003cli\u003eProbst, P. T., Mayer, M., Gupta, V., Steiner, A. M., Zhou, Z., Auernhammer, G. K., K\u0026ouml;nig, T. A. F. \u0026amp; Fery, A. Mechano-tunable chiral metasurfaces via colloidal assembly. \u003cem\u003eNat. Mater.\u003c/em\u003e \u003cstrong\u003e20\u003c/strong\u003e, 1024\u0026ndash;1028 (2021).\u003c/li\u003e\n \u003cli\u003eZhou, Z., Zhao, Z., Yu, Y., Ai, B., M\u0026ouml;hwald, H., Chiechi, R. C., Yang, J. K. W. \u0026amp; G. Zhang, From 1D to 3D: Tunable Sub-10 nm Gaps in Large Area Devices. \u003cem\u003eAdv. Mater.\u003c/em\u003e \u003cstrong\u003e28\u003c/strong\u003e, 2956-2963 (2016).\u003c/li\u003e\n \u003cli\u003eGovorov, A. O., Fan, Z., Hernandez, P., Slocik, J. M. \u0026amp; Naik, R. R. Theory of circular dichroism of nanomaterials comprising chiral molecules and nanocrystals: plasmon enhancement, dipole interactions, and dielectric effects. \u003cem\u003eNano Lett.\u003c/em\u003e\u003cstrong\u003e10\u003c/strong\u003e, 1374-1382 (2010).\u003c/li\u003e\n \u003cli\u003eGovorov, A. O. Plasmon-induced circular dichroism of a chiral molecule in the vicinity of metal nanocrystals. Application to various geometries. \u003cem\u003eJ. Phys. Chem. C\u003c/em\u003e \u003cstrong\u003e115\u003c/strong\u003e, 7914-7923 (2011).\u003c/li\u003e\n \u003cli\u003eKneer, L. M., Roller, E. M., Besteiro, L. V., Schreiber, R., Govorov, A. O. \u0026amp; Liedl, T. Circular dichroism of chiral molecules in DNA-assembled plasmonic hotspots. \u003cem\u003eACS nano\u003c/em\u003e \u003cstrong\u003e12\u003c/strong\u003e, 9110-9115 (2018).\u003c/li\u003e\n \u003cli\u003eHao, C., Xu, L., Sun, M., Ma, W., Kuang, H. \u0026amp; Xu, C. Chirality on Hierarchical Self‐Assembly of Au@AuAg Yolk\u0026ndash;Shell Nanorods into Core\u0026ndash;Satellite Superstructures for Biosensing in Human Cells. \u003cem\u003eAdv. Funct. Mater.\u003c/em\u003e \u003cstrong\u003e28\u003c/strong\u003e, 1802372 (2018).\u003c/li\u003e\n \u003cli\u003eCao, Z., Gao, H., Qiu, M., Jin, W., Deng, S., Wong, K. Y. \u0026amp; Lei, D. Chirality Transfer from Sub‐Nanometer Biochemical Molecules to Sub-Micrometer Plasmonic Metastructures: Physiochemical Mechanisms, Biosensing, and Bioimaging Opportunities. \u003cem\u003eAdv. Mater.\u003c/em\u003e \u003cstrong\u003e32\u003c/strong\u003e, 1907151 (2020).\u003c/li\u003e\n \u003cli\u003eZhang, Q., Hernandez, T., Smith, K. W., Hosseini Jebeli, S. A., Dai, A. X., Warning, L., Guo, H., Chen, D.-H., Dionne, J. A., Landes, C. F. \u0026amp; Link, S. Unraveling the origin of chirality from plasmonic nanoparticle-protein complexes. \u003cem\u003eScience\u003c/em\u003e \u003cstrong\u003e365\u003c/strong\u003e, 1475-1478 (2019).\u003c/li\u003e\n \u003cli\u003eKim, J. Y. \u0026amp; Kotov, N. A. Origin of chiroptical activity in nanorod assemblies. \u003cem\u003eScience\u003c/em\u003e \u003cstrong\u003e365\u003c/strong\u003e, 1378-1379 (2019).\u003c/li\u003e\n \u003cli\u003eLan, X., Zhou, X., McCarthy, L. A., Govorov, A. O., Liu, Y. \u0026amp; Link, S. DNA-Enabled Chiral Gold Nanoparticle\u0026ndash;Chromophore Hybrid Structure with Resonant Plasmon\u0026ndash;Exciton Coupling Gives Unusual and Strong Circular Dichroism. \u003cem\u003eJ. Am. Chem. Soc.\u003c/em\u003e \u003cstrong\u003e141\u003c/strong\u003e, 19336-19341(2019).\u003c/li\u003e\n \u003cli\u003eSteiner, A. M., Mayer, M., Seuss, M., Nikolov, S., Harris, K. D., Alexeev, A., Kuttner, C., K\u0026ouml;nig, T. A. F. \u0026amp; Fery, A. Macroscopic strain-induced transition from quasi-infinite gold nanoparticle chains to defined plasmonic oligomers. \u003cem\u003eACS nano\u003c/em\u003e \u003cstrong\u003e11\u003c/strong\u003e, 8871-8880 (2017).\u003c/li\u003e\n \u003cli\u003eGupta, V., Probst, P. T., Go\u0026szlig;ler, F. R., Steiner, A. M., Schubert, J., Brasse, Y., K\u0026ouml;nig, T. A. F. \u0026amp; Fery, A. Mechanotunable surface lattice resonances in the visible optical range by soft lithography templates and directed self-assembly. \u003cem\u003eACS Appl. Mater. Interfaces\u003c/em\u003e \u003cstrong\u003e11\u003c/strong\u003e, 28189-28196 (2019).\u003c/li\u003e\n \u003cli\u003eHanske, C., Tebbe, M., Kuttner, C., Bieber, V., Tsukruk, V. V., Chanana, M., K\u0026ouml;nig, T. A. F. \u0026amp; Fery, A. Strongly coupled plasmonic modes on macroscopic areas via template-assisted colloidal self-assembly. \u003cem\u003eNano Lett.\u003c/em\u003e \u003cstrong\u003e14\u003c/strong\u003e, 6863-6871 (2014).\u003c/li\u003e\n \u003cli\u003eMayer, M., Potapov, P. L., Pohl, D., Steiner, A. M., Schultz, J., Rellinghaus, B., Lubk, A., K\u0026ouml;nig, T. A. F. \u0026amp; Fery, A. Direct observation of plasmon band formation and delocalization in quasi-infinite nanoparticle chains. \u003cem\u003eNano Lett.\u003c/em\u003e \u003cstrong\u003e19\u003c/strong\u003e, 3854-3862 (2019).\u003c/li\u003e\n \u003cli\u003eZhu, G., Zhu, X., Fan, Q. \u0026amp; Wan, X. Raman spectra of amino acids and their aqueous solutions. \u003cem\u003eSpectrochim. Acta A Mol. Biomol. Spectrosc.\u0026nbsp;\u003c/em\u003e\u003cstrong\u003e78\u003c/strong\u003e, 1187-1195 (2011).\u003c/li\u003e\n \u003cli\u003eAbdelmoez, W. \u0026amp; Yoshida, H. Production of amino and organic acids from protein using sub-critical water technology. \u003cem\u003eInt. J. Chem. React.\u003c/em\u003e \u003cstrong\u003e11\u003c/strong\u003e, 369-384 (2013).\u003c/li\u003e\n \u003cli\u003eAlvarez-Puebla, R., Liz-Marz\u0026aacute;n, L. M. \u0026amp; García de Abajo, F. J. Light concentration at the nanometer scale. \u003cem\u003eJ. Phys. Chem. Lett.\u003c/em\u003e \u003cstrong\u003e1\u003c/strong\u003e, 2428-2434 (2010).\u003c/li\u003e\n \u003cli\u003ePazos, E., Garcia-Algar, M., Penas, C., Nazarenus, M., Torruella, A., Pazos-Perez, N., Guerrini, L., Vazquez, M. E., Garcia-Rico, E., Mascarenas, J. L. \u0026amp; Alvarez-Puebla, R. A. Surface-enhanced raman scattering surface selection rules for the proteomic liquid biopsy in real samples: Efficient detection of the oncoprotein c-MYC. \u003cem\u003eJ. Am. Chem. Soc.\u003c/em\u003e \u003cstrong\u003e138\u003c/strong\u003e, 14206-14209 (2016).\u003c/li\u003e\n \u003cli\u003eAbdelwahab, M. T., Kalyoncu, E., Onur, T., Baykara, M. Z. \u0026amp; Seker, U. O. S. Genetically-tunable mechanical properties of bacterial functional amyloid nanofibers. \u003cem\u003eLangmuir\u003c/em\u003e \u003cstrong\u003e33\u003c/strong\u003e, 4337-4345 (2017).\u003c/li\u003e\n \u003cli\u003eMoskovits, M. Surface selection rules. \u003cem\u003eJ. Chem. Phys.\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;77\u003c/strong\u003e, 4408-4416 (1982).\u003c/li\u003e\n \u003cli\u003eHanske, C., Gonz\u0026aacute;lez-Rubio, G., Hamon, C., Forment\u0026iacute;n, P., Modin, E., Chuvilin, A., Guerrero-Mart\u0026iacute;nez, A., Marsal, L. F. \u0026amp; Liz-Marzán, L. M. Large-scale plasmonic pyramidal supercrystals via templated self-assembly of monodisperse gold nanospheres. \u003cem\u003eJ. Phys. Chem. C\u0026nbsp;\u003c/em\u003e\u003cstrong\u003e121\u003c/strong\u003e, 10899-10906 (2017).\u003c/li\u003e\n \u003cli\u003eSchweikart, A., Fortini, A., Wittemann, A., Schmidt, M. \u0026amp; Fery, A. Nanoparticle assembly by confinement in wrinkles: experiment and simulations. \u003cem\u003eSoft Matter\u003c/em\u003e \u003cstrong\u003e6\u003c/strong\u003e, 5860-5863 (2010).\u003c/li\u003e\n \u003cli\u003eWang, W., Wu, F., Zhang, Y., Wei, W., Niu, W. \u0026amp; Xu, G. Boosting chiral amplification in plasmon-coupled circular dichroism using discrete silver nanorods as amplifiers. \u003cem\u003eChem. Commun.\u003c/em\u003e \u003cstrong\u003e57\u003c/strong\u003e, 7390-7393 (2021).\u003c/li\u003e\n \u003cli\u003eHao, C., Xu, L., Ma, W., Wu, X., Wang, L., Kuang, H. \u0026amp; Xu, C. Unusual circularly polarized photocatalytic activity in nanogapped gold\u0026ndash;silver chiroplasmonic nanostructures. \u003cem\u003eAdv. Funct. Mater.\u003c/em\u003e \u003cstrong\u003e25\u003c/strong\u003e, 5816-5822 (2015).\u003c/li\u003e\n \u003cli\u003eMaoz, B. M., van der Weegen, R., Fan, Z., Govorov, A. O., Ellestad, G., Berova, N. \u0026amp; Markovich, G. Plasmonic chiroptical response of silver nanoparticles interacting with chiral supramolecular assemblies. \u003cem\u003eJ. Am. Chem. Soc.\u003c/em\u003e \u003cstrong\u003e134\u003c/strong\u003e, 17807-17813 (2012).\u003c/li\u003e\n \u003cli\u003eSlocik, J. M., Govorov, A. O. \u0026amp; Naik, R. R. Plasmonic circular dichroism of peptide-functionalized gold nanoparticles. \u003cem\u003eNano Lett.\u003c/em\u003e \u003cstrong\u003e11\u003c/strong\u003e, 701-705 (2011).\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"nature-portfolio","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Nature Portfolio","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"ejp","reportingPortfolio":"","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Chirality transfer, chirality switching, high g-factor, biomolecule, colloidal assembly","lastPublishedDoi":"10.21203/rs.3.rs-1570427/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1570427/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Yet while nature effortlessly creates chiral biomolecules, the fabrication of artificial chiral nanostructures is significantly more onerous. Therefore, investigating the chirality transfer from abundant biomolecules to simple nanostructures without sophisticated three-dimensional nanofabrication is convenient and meaningful. However, in the previous studies with this goal, the biomolecules mostly acted as structurally chiral templates to permanently break the mirror symmetry of nanostructures, whose chirality transfer was irreversible and thus lacking in flexibility in applications. Here we discovered an in-situ biomolecule-stretching strategy to realize the highly efficient (dissymmetry factor 0.2) and reversible chirality transfer from biomolecules to nanoparticles for the first time, based on a Coulombic “field effect” rather than a traditional “structural effect”. Due to this unique “field effect”, the mirror symmetry of nanostructures is well maintained. Thus, the chirality can be smartly reversed over 100 cycles to meet various requirements of modern chiral devices. Our results unravel how achiral plasmons acquire chirality from a biomolecule efficiently and reversibly, interpreting the intimate interaction between biomolecules and plasmonic fields.","manuscriptTitle":"Highly efficient and switchable chirality transfer between protein and achiral plasmonic assemblies","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-05 11:40:17","doi":"10.21203/rs.3.rs-1570427/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"nature-materials","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"nmat","sideBox":"Learn more about [Nature Materials](http://www.nature.com/nmat/)","snPcode":"","submissionUrl":"","title":"Nature Materials","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature Research","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"30a95c99-e1f5-4ff6-ad16-bb139a985978","owner":[],"postedDate":"May 5th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":45481581,"name":"Physical sciences/Materials science/Nanoscale materials/Metamaterials"},{"id":45481582,"name":"Physical sciences/Nanoscience and technology/Nanobiotechnology/Biosensors"},{"id":45481583,"name":"Physical sciences/Materials science/Biomaterials/Biomaterials \u0026#x2013; proteins"}],"tags":[],"updatedAt":"2026-04-16T07:17:02+00:00","versionOfRecord":{"articleIdentity":"rs-1570427","link":"https://doi.org/10.1038/s41563-026-02586-7","journal":{"identity":"nature-materials","isVorOnly":false,"title":"Nature Materials"},"publishedOn":"2026-04-15 04:00:00","publishedOnDateReadable":"April 15th, 2026"},"versionCreatedAt":"2025-05-05 11:40:17","video":"","vorDoi":"10.1038/s41563-026-02586-7","vorDoiUrl":"https://doi.org/10.1038/s41563-026-02586-7","workflowStages":[]},"version":"v1","identity":"rs-1570427","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1570427","identity":"rs-1570427","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}