Toward a Geochemical Model for Directional Chiral Selection: Peptide β-Sheet Nucleation at Chiral Mineral–Seawater Interfaces as a Candidate Mechanism

Toward a Geochemical Model for Directional Chiral Selection: Peptide β-Sheet Nucleation at Chiral Mineral–Seawater Interfaces as a Candidate Mechanism | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Toward a Geochemical Model for Directional Chiral Selection: Peptide β-Sheet Nucleation at Chiral Mineral–Seawater Interfaces as a Candidate Mechanism Masato MIYAKE This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9392776/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract The origin of biological homochirality—the near-exclusive use of L-amino acids in proteins—remains one of the most persistent unsolved problems in studies of life’s emergence. Here we present a conceptual geochemical model in which peptide β-sheet self-assembly at chiral mineral–seawater interfaces could generate directional kinetic selection of chirality. We propose that this mechanism may have contributed to the initial enantiomeric bias that preceded, and was subsequently amplified by, autocatalytic and evolutionary processes. We distinguish three conceptually distinct levels of the homochirality problem: (i) the preference for homochiral over racemic assemblies; (ii) the directional selection of a specific enantiomer (L vs. D) at individual mineral surface sites; and (iii) the propagation of local enrichment to planetary-scale homochirality. The present work focuses on level (ii), proposing chiral mineral surface structures as a candidate source of directional bias, while acknowledging that levels (i) and (iii) involve additional mechanisms. β-sheet assemblies are selected as the focus because their characteristic interstrand spacing (~ 4.7 Å, as measured by X-ray diffraction of cross-β structures) faces the mineral surface directly, enabling potential two-dimensional geometric templating—a mode of interaction geometrically less accessible for α-helices. Several minerals abundant on the early Earth present surface lattice periodicities in a broadly comparable range. Crucially, mineral crystal faces can present intrinsically chiral surface structures that interact enantioselectively with adsorbed amino acids, as demonstrated experimentally for calcite. We hypothesize that analogous chiral surface features on iron–sulfur minerals, combined with asymmetric coordination environments involving hydrated Mg²⁺ ions, could create conditions favoring one enantiomer during peptide nucleation. We derive the minimum activation free-energy difference |ΔΔG‡| required to achieve biologically relevant chiral enrichment as a function of environmental parameters, and map this against current experimental and computational measurement thresholds. This analysis provides specific quantitative targets for future experimental validation. We emphasize that the model remains at a conceptual stage: direct evidence for enantioselective peptide nucleation on iron–sulfur minerals is not yet available, and the propagation of local enrichment to global homochirality remains an open problem. Homochirality amino acid chirality mineral surface peptide self-assembly β-sheet nucleation prebiotic chemistry origin of life Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction The universal use of L-amino acids in biological proteins represents one of the central unresolved problems in origin-of-life research. Modern biological systems employ almost exclusively L-amino acids in proteins and D-sugars in nucleic acids, yet abiotic chemical synthesis typically produces racemic mixtures [ 1 – 3 ]. Extraterrestrial evidence further highlights this problem: amino acids recovered from carbonaceous meteorites and returned asteroid samples show L/D ratios close to unity [ 4 – 7 ], implying that the decisive processes leading to biological homochirality most likely occurred within terrestrial environments. Several mechanisms have been proposed for prebiotic chiral symmetry breaking, including asymmetric photochemistry, parity-violating weak interactions, enantioselective crystallization, and nonlinear amplification [ 8 – 12 ]. Autocatalytic reaction networks have attracted particular attention: the Soai reaction demonstrates that autocatalytic processes can generate highly enantioenriched products from nearly racemic starting conditions [ 13 ]. Theoretical work by Kauffman explored how self-organizing catalytic networks may arise spontaneously in sufficiently complex chemical systems [ 14 ], and Lee, Granja, Martinez, Severin, and Ghadiri experimentally demonstrated the first self-replicating peptide system [ 15 ]. Subsequent work from the same group demonstrated chiroselective amplification, preferentially producing homochiral products from racemic precursor fragments [ 16 ]. However, a critical gap remains: neither Kauffman’s theoretical model nor Ghadiri’s experimental system explains the initial direction of chiral selection—why L-amino acids rather than D-amino acids came to dominate terrestrial biology. The present study addresses this gap by proposing chiral mineral–seawater interfaces as a candidate source of directional bias. Distinguishing three levels of the homochirality problem It is essential to distinguish three conceptually distinct problems that are sometimes conflated (Fig. 1 ). Level 1 : Why do biological systems use amino acids of a single handedness rather than racemic mixtures? This is addressed by the thermodynamics and kinetics of peptide self-assembly. Level 2 : Why specifically L-amino acids on Earth? This requires a mechanism for directional selection, which is the central proposal of this work. Level 3 : How was local enantiomeric enrichment propagated to planetary-scale homochirality? This likely involves autocatalytic amplification [ 15 , 16 ], selective degradation, and spatial propagation, and remains an open problem beyond the scope of this hypothesis. Why β-sheets? Among peptide secondary structures, we focus on β-sheets for three specific structural reasons (Fig. 2 ). First, β-sheets are formed through intermolecular hydrogen bonds between separate peptide chains, making them inherently supramolecular structures. This is in contrast to α-helices, which are stabilized by intramolecular hydrogen bonds within a single chain. The supramolecular character of β-sheets makes them directly relevant to the aggregation and nucleation processes central to this model. Second, the ~ 4.7 Å interstrand spacing of cross-β structures [ 17 – 20 ] faces the mineral surface perpendicularly, enabling potential two-dimensional geometric templating. By contrast, the periodicity of an α-helix (~ 5.4 Å pitch) runs along the helix axis, which lies parallel to the surface upon adsorption, making it geometrically less accessible for surface-mediated templating. Third, β-sheet-like amyloid aggregates form spontaneously even from very short peptides—including dipeptides and tripeptides [ 21 – 24 ]—suggesting that β-sheet formation could have occurred with the limited peptide repertoire available under prebiotic conditions [ 25 – 28 ]. Stable α-helix formation typically requires longer peptide chains (~ 10 + residues). We do not claim that β-sheets were the only self-assembling motif in prebiotic chemistry. The present focus reflects a specific structural hypothesis about surface-mediated chiral selection that depends on the geometric relationship between peptide periodicity and mineral surface lattice spacing. A connection between peptide assembly and early Earth geochemistry arises from the abundance of iron–sulfur minerals in Archaean environments [ 29 – 31 ]. These minerals have been widely discussed in origin-of-life research because many modern metabolic enzymes rely on Fe–S clusters [ 32 – 34 ]. The hypothesis proposed here links chiral mineral surface geometry, heterometal coordination chemistry, peptide β-sheet self-assembly, and the autocatalytic amplification framework of Kauffman and Ghadiri. We stress that the present proposal is hypothesis-generating rather than explanatory proof. Geochemical Context of Early Earth Prior to the Great Oxidation Event (~ 2.4 Ga), the atmosphere and oceans were largely anoxic, allowing dissolved ferrous iron (Fe²⁺) to accumulate at concentrations of tens to hundreds of micromolar [ 29 – 31 ]. Under such conditions, iron–sulfur minerals including mackinawite (FeS), greigite (Fe₃S₄), and pyrite (FeS₂) formed through sequential mineralogical transformations [ 35 ]. Iron–sulfur minerals have long been considered central to origin-of-life models [ 32 – 34 ]. Early ocean chemistry was also strongly influenced by abundant dissolved Mg²⁺, which retains a well-defined hydration shell of six coordinated water molecules [ 36 ]. At mineral–seawater interfaces, the coordination environment is fundamentally asymmetric: a rigid mineral lattice on one side and a dynamic, ion-rich aqueous phase on the other. However, the specific role of Mg²⁺ hydration in modulating peptide–mineral interactions has not been characterized experimentally for iron–sulfur systems. Greigite is relevant because its inverse spinel crystal structure (a ≈ 9.88 Å [ 37 ]) yields some surface terminations with nearest-neighbor spacings near 5.0 Å, broadly comparable to the 4.7 Å β-sheet periodicity. However, as discussed in the Mineral Lattice Compatibility section, this comparison requires substantial qualification regarding crystal face specificity, surface reconstruction, and intervening water layers. Chiral Asymmetry at Mineral Surfaces Experimental evidence from calcite Hazen, Filley, and Goodfriend [ 38 ] demonstrated that calcite (CaCO₃) can selectively adsorb L- and D-amino acids on mirror-related scalenohedral {21̔1} crystal growth surfaces. Subsequent computational work estimated enantiospecific binding energy differences of approximately 8 kcal/mol (~ 33 kJ/mol) for aspartic acid on calcite [ 39 ], arising from a difference between three versus two strong bonding contacts depending on molecular handedness (Fig. 3 ). This selectivity was enhanced on surfaces with terraced growth textures, indicating that step edges and kink sites play an important role. As reviewed by Hazen and Sholl [ 39 ], chiral surface structures are widespread among common minerals [ 40 , 41 ]. The adsorption and polymerization of amino acids on mineral surfaces has been extensively studied [ 42 , 43 ]. Any crystal face whose surface atomic arrangement lacks mirror symmetry has the potential for enantioselective adsorption. Extrapolation to iron–sulfur minerals: scope and limitations A central assumption of the present model is that iron–sulfur minerals also present chiral surface features capable of enantioselective interactions. This assumption is physically reasonable but has not been experimentally validated. No measurements of enantioselective amino acid adsorption on iron–sulfur mineral surfaces have been reported. Furthermore, the calcite experiments measured adsorption of individual amino acids, whereas the present model concerns nucleation of peptide β-sheet assemblies—a substantially more complex process. This gap between single-amino-acid adsorption on calcite and peptide supramolecular assembly on iron–sulfur minerals represents the most significant unvalidated step in the present hypothesis. Direction of selection: contingent rather than universal The direction of chiral selection (L vs. D) is determined by local geological conditions. On Earth, the particular combination of minerals, crystal face orientations, and solution chemistry may have generated a net bias toward L-amino acids. On another planet, the opposite enantiomer could be selected. This prediction distinguishes the present model from mechanisms invoking universal physical asymmetries. A critical unresolved question is how local biases—which could favor L at some sites and D at others—were integrated into globally uniform L-amino acid preference. The present model addresses only the generation of directional bias at individual sites; global fixation requires additional processes. Mechanistic Model The model is structured around the three conceptually distinct levels introduced in Fig. 1 . The free energy of peptide assemblies can be conceptually decomposed as: G_int = G_HB + G_hydrophobic + G_steric + G_solvation + G_surface For Level 1 (homochiral vs. racemic), the comparison involves primarily G_HB, G_steric, and G_solvation [ 44 – 47 ]. For Level 2 (L vs. D), G_surface introduces a direction-dependent contribution from chiral mineral surface contacts [ 38 , 39 ]. Nucleation kinetics From transition-state theory, the nucleation rate constant depends exponentially on the free-energy barrier [ 48 – 50 ]: k = k₀ exp(–ΔG‡ / RT) If, at a specific chiral mineral surface site, an L-type homochiral nucleus has a slightly lower activation barrier than a D-type nucleus: k_L / k_D = exp(–(ΔG‡_L – ΔG‡_D) / RT) This exponential dependence converts small energetic differences into potentially significant rate differences. Connection to autocatalytic amplification Mineral-mediated selection alone may be insufficient to produce macroscopic homochirality, because different surface sites may favor different enantiomers and the per-site bias may be small. The autocatalytic amplification framework of Ghadiri and colleagues [ 16 ] provides the necessary positive feedback: once any local environment achieves sufficient enantiomeric excess, chiroselective self-replication can lock in and amplify that excess. Mineral-mediated directional selection and autocatalytic amplification are thus complementary: the former provides the initial directional seed, the latter amplifies it. Mineral Lattice Compatibility The ~ 4.7 Å inter-strand spacing of cross-β structures is robust across diverse peptide sequences [ 17 – 19 ]. Several candidate minerals exhibit surface lattice periodicities in a comparable range (Supplementary Table S1 ). However, the comparison requires qualification: surface periodicities depend on the specific crystal face exposed, surface reconstruction can alter effective spacings, and no surface characterization of greigite in aqueous environments has been reported. The broad range of 4–6 Å cited for mineral spacings encompasses both well-matched and poorly matched values. Furthermore, in aqueous solution, intervening water layers may partially transmit or completely attenuate the geometric influence of the underlying lattice. Whether the mineral lattice periodicity is ‘felt’ by an adsorbed peptide assembly through intervening water layers is an open question. Quantitative Analysis: Required Energetic Bias and Experimental Measurement Thresholds A key quantitative question for the present model is: what minimum activation free-energy difference |ΔΔG‡| is required to achieve biologically relevant chiral enrichment within the available geological time, and is this difference within reach of current or foreseeable experimental and computational methods? This analysis provides specific targets for future experimental validation. Derivation of the required energetic bias Consider a system of peptide assemblies undergoing repeated nucleation–dissolution cycles at chiral mineral surfaces. Let α = k_L/k_D be the per-cycle enrichment factor. After N_eff effective cycles: (L/D)_final = (L/D)₀ × α^N_eff where N_eff = η × N is the effective number of selection cycles, N is the total number of physical cycles, and η is an efficiency factor (0 < η ≤ 1) that accounts for environmental noise, sign reversal between L-selecting and D-selecting surface sites, dilution, hydrolysis, racemization, and competing reactions. The efficiency factor η is the most uncertain parameter in the model and is likely to be very small in realistic prebiotic environments. Setting (L/D)_final to the target enrichment and solving for the required per-cycle bias ε = α – 1: ε = ln(target) / N_eff From transition-state theory, the corresponding activation free-energy difference is: |ΔΔG‡| = ε × RT Parameter space analysis Figure 4 maps the required |ΔΔG‡| as a function of the efficiency factor η for three representative cycling frequencies (1-hour, 1-day, and 1-year intervals), with T = 333 K (60°C, representative of warm hydrothermal environments [51,52]), available geological time = 5 × 10⁸ years (from Earth formation to the earliest evidence of life), and target L/D = 10⁶ (effective homochirality). Interpretation and experimental implications Several conclusions emerge from this analysis: (1) The theoretical minimum bias is extraordinarily small. For optimistic to moderate scenarios (η = 10⁻¹ to 10⁻²), the required |ΔΔG‡| is 10⁻⁷ to 10⁻⁵ kJ/mol—many orders of magnitude below thermal noise (RT ≈ 2.77 kJ/mol at 333 K). This demonstrates that the energetic threshold is not the limiting factor; rather, the critical question is whether a net directional bias survives environmental averaging. (2) Conservative scenarios approach experimental limits. For η = 10⁻⁴ with daily cycling, the required |ΔΔG‡| is approximately 10⁻² to 10⁻¹ kJ/mol, which overlaps with the precision of state-of-the-art computational chemistry methods (DFT/MD). This suggests that molecular dynamics simulations of peptide adsorption on well-defined chiral mineral surfaces could provide a meaningful test of the hypothesis. (3) Pessimistic scenarios require larger biases. For η = 10⁻⁶ with annual cycling, the required |ΔΔG‡| reaches 10° to 10¹ kJ/mol, well within the range of experimental calorimetry. In this regime, direct experimental measurement of enantioselective adsorption energetics on iron–sulfur mineral surfaces would provide a definitive test. Importantly, the measured enantiospecific binding energy difference for aspartic acid on calcite (~ 33 kJ/mol [ 38 , 39 ]) is orders of magnitude larger than the required |ΔΔG‡| in any scenario except the most pessimistic. This indicates that mineral surface enantioselectivity of the required magnitude is physically achievable—though the relevant quantity for the present model is the much smaller difference in nucleation barriers for supramolecular assemblies, not individual molecular binding energies. Limitations of the α^N_eff calculation This analysis rests on three idealizations: (i) that each cycle produces a directional bias of the same sign, whereas in reality different surface sites may favor different enantiomers; (ii) that there are no back-reactions, dilution, or loss between cycles; (iii) that environmental noise does not overwhelm the signal. The efficiency factor η is introduced to account for these effects in an aggregate way, but its value is unknown and may itself vary over orders of magnitude depending on environmental conditions. We therefore present this analysis not as a quantitative prediction, but as a framework for identifying the experimental measurements needed to test the hypothesis. Discussion What the model claims and does not claim Established (a) Chiral mineral surface features exist and can enantioselectively adsorb amino acids (demonstrated for calcite [ 38 , 39 ]). (b) Peptides self-assemble into β-sheet structures with ~ 4.7 Å periodicity [ 17 – 19 ]. (c) Homochiral peptide assemblies are generally more ordered than racemic mixtures [ 53 – 55 ]. (d) Autocatalytic peptide replicators can amplify existing enantiomeric excesses [ 15 , 16 ]. Proposed but not yet tested (a) Iron–sulfur mineral surfaces present chiral features capable of enantioselective interactions with peptides. (b) β-sheet nucleation kinetics are measurably influenced by chiral mineral surface geometry. (c) The geometric match between β-sheet periodicity and mineral surface spacing is functionally significant in aqueous environments. Beyond scope (a) How local chiral enrichment was propagated to planetary-scale homochirality. (b) The specific geological scenario that produced a net L-bias. Strengths The model integrates independently established physical phenomena into a coherent framework that identifies a specific physical mechanism for directional chiral selection—a gap in existing theories. The energetic requirements are modest, and the parameter space analysis (Fig. 4 ) provides concrete experimental targets. The model is compatible with the autocatalytic amplification framework [ 14 – 16 ] and generates testable predictions distinguishable from universal-asymmetry models [ 8 , 9 ]. Limitations The most significant limitation is the absence of direct experimental evidence for the central hypothesis: enantioselective peptide β-sheet nucleation on iron–sulfur mineral surfaces. The local-to-global propagation problem remains unresolved. The role of Mg²⁺ and structured interfacial water, while conceptually attractive, remains speculative. The idealized amplification calculation overstates effective enrichment by neglecting environmental noise and spatial heterogeneity. Experimental testability The parameter space analysis (Fig. 4 ) suggests a prioritized experimental program: (1) Enantioselective amino acid adsorption on iron–sulfur minerals Repeating Hazen’s calcite experiments [ 38 ] with greigite, mackinawite, or pyrite would directly test the key assumption. (2) Molecular dynamics simulations DFT/MD calculations of peptide adsorption on hydrated iron–sulfur surfaces could estimate enantiospecific binding energies and nucleation barriers. Figure 4 indicates that computational precision of ~ 0.01 kJ/mol would be informative for moderate-efficiency scenarios. (3) Peptide nucleation kinetics on chiral mineral surfaces Using quartz crystal microbalance, AFM, or surface-sensitive spectroscopy to compare L- vs. D-peptide aggregation kinetics on chiral crystal faces [ 56 – 58 ]. (4) Cyclic enrichment experiments Microfluidic wet–dry cycling reactors to test whether repeated assembly–disassembly cycles on chiral mineral surfaces produce measurable enantiomeric enrichment [ 59 ]. Astrobiological implications If mineral-surface-mediated directional selection operates as proposed, biological homochirality reflects contingent planetary geochemistry in its specific direction. Discovery of D-amino acid-based life on another planet would support contingent selection mechanisms. The model predicts that homochirality is a predictable consequence of generic geochemical processes, even though its specific direction would vary by planet. Conclusion We have presented a conceptual model proposing that chiral mineral–seawater interfaces could have contributed to the initial directional selection of amino acid chirality. The model addresses a specific gap in existing theories: the origin of directional chiral bias. We emphasize the distinction between three levels of the problem (homochiral vs. racemic; L vs. D direction; local vs. global) and contribute primarily to the second. The quantitative parameter space analysis provides specific experimental targets: for realistic efficiency factors, the required energetic biases range from computationally accessible (~ 0.01 kJ/mol) to experimentally measurable (~ 0.1 kJ/mol), depending on the assumed environmental noise and cycling frequency. The known enantiospecific binding energy on calcite (~ 33 kJ/mol) far exceeds these thresholds, establishing the physical plausibility of the mechanism. The most significant limitation remains the absence of direct experimental evidence for enantioselective peptide nucleation on iron–sulfur mineral surfaces. We have outlined a prioritized experimental program to test the model’s key predictions, guided by the parameter space analysis of Fig. 4 . Declarations Competing Interests The author declares no competing financial or non-financial interests. Funding This research received no specific funding from any agency in the public, commercial, or not-for-profit sectors. Author Contributions M. Miyake is the sole author and is responsible for all aspects of this work, including conceptualization, theoretical development, quantitative analysis, and manuscript preparation. Use of AI Tools In accordance with Springer Nature’s policy on the use of large language models (LLMs), the author discloses that an AI assistant (Anthropic Claude, Claude Opus 4) was used during manuscript preparation. The AI tool was used for the following purposes: assistance with literature search and organization, structural and organizational suggestions for manuscript drafting, verification of mathematical expressions, generation of figure drafts, and English language editing. All scientific hypotheses, intellectual content, theoretical reasoning, and interpretive conclusions are solely those of the author. The AI tool does not meet the journal’s criteria for authorship, as it cannot take accountability for the work, and is therefore not listed as an author. Data Availability This is a theoretical/conceptual paper. No experimental data were generated. All parameters used in the quantitative analysis are stated explicitly in the text and figures. Ethics, Consent to Participate, and Consent to Publish Not applicable. Clinical Trial Number Not applicable. References Miller SL (1953) A production of amino acids under possible primitive Earth conditions. 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Science 326:1533–1537 Forsythe JG et al (2015) Ester-mediated amide bond formation driven by wet–dry cycles. Angew Chem Int Ed 54:9871–9875 Additional Declarations No competing interests reported. Supplementary Files MiyakeSupplementary.docx MiyakeSupplementaryrevised.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-9392776","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":624983860,"identity":"8314ec79-b299-40ce-89c1-04aca02d369b","order_by":0,"name":"Masato MIYAKE","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5klEQVRIiWNgGAWjYDADNgYGZgaGCoYEIIPBgKDyA3AtZ0jRwgDSwtjGkEBQtW778YefP1QwRPNJJD82+DjvcB4fewNDcQEeLWZncowlDpxhyG2TSDNOnLktrZiN5wCD8Qx8Wg7kMEgcbPsP1JJgfJh3m00ikMFgzINPy/nnj38cbAPZkv758N85EkRouZFgJgHRkmOczNhAjC033phZnAH5hedNsWHPMZBfDjbg98v59Mc3KioYcue3p2+W+FFzOE++vfmYMb4QQwCBBBiLsc2YKB0M/AfgTObHxGkZBaNgFIyCEQIAH1JOWpwaanUAAAAASUVORK5CYII=","orcid":"","institution":"National Institute of Advanced Industrial Science and Technology","correspondingAuthor":true,"prefix":"","firstName":"Masato","middleName":"","lastName":"MIYAKE","suffix":""}],"badges":[],"createdAt":"2026-04-12 08:38:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9392776/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9392776/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":108092460,"identity":"ab19f249-f37a-4d6b-9283-295d1feac1ef","added_by":"auto","created_at":"2026-04-29 09:33:06","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":239276,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThree levels of the homochirality problem. \u003c/strong\u003eEach level requires distinct evidence and mechanisms. The present study focuses on Level 2 (directional selection), proposing chiral mineral surfaces as a candidate mechanism. Level 3 (local-to-global propagation) is acknowledged as an unresolved problem requiring additional processes.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-9392776/v1/1bc633f48f8678b8e47bf681.png"},{"id":108181836,"identity":"8578bfbc-e77c-4980-a5cf-e4081f3e06ac","added_by":"auto","created_at":"2026-04-30 08:58:57","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":156666,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eWhy β-sheets are geometrically suited for mineral surface templating. \u003c/strong\u003e(A) β-sheet interstrand spacing (~4.7 Å) faces the mineral surface directly, allowing potential two-dimensional geometric matching. (B) α-helix pitch (~5.4 Å) runs along the helix axis parallel to the surface, limiting surface-mediated templating. This geometric distinction is the primary reason for focusing on β-sheets in the present model.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-9392776/v1/bc6fe5ec263cebb68743f2b8.png"},{"id":108092462,"identity":"a96399c9-c17d-4058-8b89-093dfc02b8ff","added_by":"auto","created_at":"2026-04-29 09:33:06","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":246749,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAsymmetric coordination of L- and D-peptides at a chiral mineral surface site. \u003c/strong\u003e(A) An L-peptide achieves three-point contact with a chiral kink site, yielding a lower nucleation barrier. (B) The mirror-image D-peptide achieves only two-point contact at the same site, yielding a higher barrier. This schematic is based by analogy on the calcite–aspartic acid system [38,39], where the 3-vs-2 contact difference was experimentally demonstrated. For Fe–S minerals, this interaction is hypothesized but not yet measured.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-9392776/v1/4af3d586a177a1182605277c.png"},{"id":108092465,"identity":"bdc5f42d-16da-4912-ae71-aac1faacf634","added_by":"auto","created_at":"2026-04-29 09:33:06","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":344338,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eParameter space map: required |ΔΔG‡| versus efficiency factor η. \u003c/strong\u003eSolid curves show the minimum activation free-energy difference required to achieve L/D = 10⁶ within 5 × 10⁸ years, for three cycling frequencies. Horizontal lines indicate approximate measurement thresholds for isothermal titration calorimetry / differential scanning calorimetry (ITC/DSC, ~0.1 kJ/mol) and density functional theory / molecular dynamics calculations (DFT/MD, ~0.01 kJ/mol). Labeled points represent illustrative scenarios. The region above the ITC/DSC line is in principle experimentally testable; the region between the two lines is accessible to computational chemistry; the region below both lines is beyond current detection limits. T = 333 K; target L/D = 10⁶.\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-9392776/v1/b6fc21234a05e057ac97f346.png"},{"id":108183813,"identity":"5cfd03c3-4598-4dec-b28d-72a08acb0102","added_by":"auto","created_at":"2026-04-30 09:02:53","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1061846,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9392776/v1/bd50d408-d832-4019-93db-bc561db8d11c.pdf"},{"id":108092459,"identity":"06176d9c-ec97-4a68-9ae9-ea1d9dc47580","added_by":"auto","created_at":"2026-04-29 09:33:06","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":15665,"visible":true,"origin":"","legend":"","description":"","filename":"MiyakeSupplementary.docx","url":"https://assets-eu.researchsquare.com/files/rs-9392776/v1/5bd6bb844528f27ad57c7ec5.docx"},{"id":108092461,"identity":"9413d53f-b8cb-40ce-b053-539ee350696c","added_by":"auto","created_at":"2026-04-29 09:33:06","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":15599,"visible":true,"origin":"","legend":"","description":"","filename":"MiyakeSupplementaryrevised.docx","url":"https://assets-eu.researchsquare.com/files/rs-9392776/v1/e1fa0ae4c2998e2e4dc385dd.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Toward a Geochemical Model for Directional Chiral Selection: Peptide β-Sheet Nucleation at Chiral Mineral–Seawater Interfaces as a Candidate Mechanism","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe universal use of L-amino acids in biological proteins represents one of the central unresolved problems in origin-of-life research. Modern biological systems employ almost exclusively L-amino acids in proteins and D-sugars in nucleic acids, yet abiotic chemical synthesis typically produces racemic mixtures [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Extraterrestrial evidence further highlights this problem: amino acids recovered from carbonaceous meteorites and returned asteroid samples show L/D ratios close to unity [\u003cspan additionalcitationids=\"CR5 CR6\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], implying that the decisive processes leading to biological homochirality most likely occurred within terrestrial environments.\u003c/p\u003e \u003cp\u003eSeveral mechanisms have been proposed for prebiotic chiral symmetry breaking, including asymmetric photochemistry, parity-violating weak interactions, enantioselective crystallization, and nonlinear amplification [\u003cspan additionalcitationids=\"CR9 CR10 CR11\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Autocatalytic reaction networks have attracted particular attention: the Soai reaction demonstrates that autocatalytic processes can generate highly enantioenriched products from nearly racemic starting conditions [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Theoretical work by Kauffman explored how self-organizing catalytic networks may arise spontaneously in sufficiently complex chemical systems [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], and Lee, Granja, Martinez, Severin, and Ghadiri experimentally demonstrated the first self-replicating peptide system [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Subsequent work from the same group demonstrated chiroselective amplification, preferentially producing homochiral products from racemic precursor fragments [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHowever, a critical gap remains: neither Kauffman\u0026rsquo;s theoretical model nor Ghadiri\u0026rsquo;s experimental system explains the \u003cem\u003einitial direction\u003c/em\u003e of chiral selection\u0026mdash;why L-amino acids rather than D-amino acids came to dominate terrestrial biology. The present study addresses this gap by proposing chiral mineral\u0026ndash;seawater interfaces as a candidate source of directional bias.\u003c/p\u003e\n\u003ch3\u003eDistinguishing three levels of the homochirality problem\u003c/h3\u003e\n\u003cp\u003eIt is essential to distinguish three conceptually distinct problems that are sometimes conflated (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). \u003cb\u003eLevel 1\u003c/b\u003e: Why do biological systems use amino acids of a single handedness rather than racemic mixtures? This is addressed by the thermodynamics and kinetics of peptide self-assembly. \u003cb\u003eLevel 2\u003c/b\u003e: Why specifically L-amino acids on Earth? This requires a mechanism for directional selection, which is the central proposal of this work. \u003cb\u003eLevel 3\u003c/b\u003e: How was local enantiomeric enrichment propagated to planetary-scale homochirality? This likely involves autocatalytic amplification [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], selective degradation, and spatial propagation, and remains an open problem beyond the scope of this hypothesis.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eWhy β-sheets?\u003c/h2\u003e \u003cp\u003eAmong peptide secondary structures, we focus on β-sheets for three specific structural reasons (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). First, β-sheets are formed through intermolecular hydrogen bonds between separate peptide chains, making them inherently supramolecular structures. This is in contrast to α-helices, which are stabilized by intramolecular hydrogen bonds within a single chain. The supramolecular character of β-sheets makes them directly relevant to the aggregation and nucleation processes central to this model. Second, the ~\u0026thinsp;4.7 \u0026Aring; interstrand spacing of cross-β structures [\u003cspan additionalcitationids=\"CR18 CR19\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] faces the mineral surface perpendicularly, enabling potential two-dimensional geometric templating. By contrast, the periodicity of an α-helix (~\u0026thinsp;5.4 \u0026Aring; pitch) runs along the helix axis, which lies parallel to the surface upon adsorption, making it geometrically less accessible for surface-mediated templating. Third, β-sheet-like amyloid aggregates form spontaneously even from very short peptides\u0026mdash;including dipeptides and tripeptides [\u003cspan additionalcitationids=\"CR22 CR23\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u0026mdash;suggesting that β-sheet formation could have occurred with the limited peptide repertoire available under prebiotic conditions [\u003cspan additionalcitationids=\"CR26 CR27\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Stable α-helix formation typically requires longer peptide chains (~\u0026thinsp;10\u0026thinsp;+\u0026thinsp;residues).\u003c/p\u003e \u003cp\u003eWe do not claim that β-sheets were the only self-assembling motif in prebiotic chemistry. The present focus reflects a specific structural hypothesis about surface-mediated chiral selection that depends on the geometric relationship between peptide periodicity and mineral surface lattice spacing.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eA connection between peptide assembly and early Earth geochemistry arises from the abundance of iron\u0026ndash;sulfur minerals in Archaean environments [\u003cspan additionalcitationids=\"CR30\" citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. These minerals have been widely discussed in origin-of-life research because many modern metabolic enzymes rely on Fe\u0026ndash;S clusters [\u003cspan additionalcitationids=\"CR33\" citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. The hypothesis proposed here links chiral mineral surface geometry, heterometal coordination chemistry, peptide β-sheet self-assembly, and the autocatalytic amplification framework of Kauffman and Ghadiri. We stress that the present proposal is hypothesis-generating rather than explanatory proof.\u003c/p\u003e \u003c/div\u003e"},{"header":"Geochemical Context of Early Earth","content":"\u003cp\u003ePrior to the Great Oxidation Event (~\u0026thinsp;2.4 Ga), the atmosphere and oceans were largely anoxic, allowing dissolved ferrous iron (Fe\u0026sup2;⁺) to accumulate at concentrations of tens to hundreds of micromolar [\u003cspan additionalcitationids=\"CR30\" citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Under such conditions, iron\u0026ndash;sulfur minerals including mackinawite (FeS), greigite (Fe₃S₄), and pyrite (FeS₂) formed through sequential mineralogical transformations [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Iron\u0026ndash;sulfur minerals have long been considered central to origin-of-life models [\u003cspan additionalcitationids=\"CR33\" citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eEarly ocean chemistry was also strongly influenced by abundant dissolved Mg\u0026sup2;⁺, which retains a well-defined hydration shell of six coordinated water molecules [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. At mineral\u0026ndash;seawater interfaces, the coordination environment is fundamentally asymmetric: a rigid mineral lattice on one side and a dynamic, ion-rich aqueous phase on the other. However, the specific role of Mg\u0026sup2;⁺ hydration in modulating peptide\u0026ndash;mineral interactions has not been characterized experimentally for iron\u0026ndash;sulfur systems.\u003c/p\u003e \u003cp\u003eGreigite is relevant because its inverse spinel crystal structure (a\u0026thinsp;\u0026asymp;\u0026thinsp;9.88 \u0026Aring; [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]) yields some surface terminations with nearest-neighbor spacings near 5.0 \u0026Aring;, broadly comparable to the 4.7 \u0026Aring; β-sheet periodicity. However, as discussed in the Mineral Lattice Compatibility section, this comparison requires substantial qualification regarding crystal face specificity, surface reconstruction, and intervening water layers.\u003c/p\u003e"},{"header":"Chiral Asymmetry at Mineral Surfaces","content":"\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eExperimental evidence from calcite\u003c/h2\u003e \u003cp\u003eHazen, Filley, and Goodfriend [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e] demonstrated that calcite (CaCO₃) can selectively adsorb L- and D-amino acids on mirror-related scalenohedral {21̔1} crystal growth surfaces. Subsequent computational work estimated enantiospecific binding energy differences of approximately 8 kcal/mol (~\u0026thinsp;33 kJ/mol) for aspartic acid on calcite [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e], arising from a difference between three versus two strong bonding contacts depending on molecular handedness (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). This selectivity was enhanced on surfaces with terraced growth textures, indicating that step edges and kink sites play an important role.\u003c/p\u003e \u003cp\u003eAs reviewed by Hazen and Sholl [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e], chiral surface structures are widespread among common minerals [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. The adsorption and polymerization of amino acids on mineral surfaces has been extensively studied [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. Any crystal face whose surface atomic arrangement lacks mirror symmetry has the potential for enantioselective adsorption.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eExtrapolation to iron–sulfur minerals: scope and limitations\u003c/h3\u003e\n\u003cp\u003eA central assumption of the present model is that iron\u0026ndash;sulfur minerals also present chiral surface features capable of enantioselective interactions. This assumption is physically reasonable but \u003cem\u003ehas not been experimentally validated.\u003c/em\u003e No measurements of enantioselective amino acid adsorption on iron\u0026ndash;sulfur mineral surfaces have been reported. Furthermore, the calcite experiments measured adsorption of individual amino acids, whereas the present model concerns nucleation of peptide β-sheet assemblies\u0026mdash;a substantially more complex process. This gap between single-amino-acid adsorption on calcite and peptide supramolecular assembly on iron\u0026ndash;sulfur minerals represents the most significant unvalidated step in the present hypothesis.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eDirection of selection: contingent rather than universal\u003c/h2\u003e \u003cp\u003eThe direction of chiral selection (L vs. D) is determined by local geological conditions. On Earth, the particular combination of minerals, crystal face orientations, and solution chemistry may have generated a net bias toward L-amino acids. On another planet, the opposite enantiomer could be selected. This prediction distinguishes the present model from mechanisms invoking universal physical asymmetries. A critical unresolved question is how local biases\u0026mdash;which could favor L at some sites and D at others\u0026mdash;were integrated into globally uniform L-amino acid preference. The present model addresses only the generation of directional bias at individual sites; global fixation requires additional processes.\u003c/p\u003e \u003c/div\u003e"},{"header":"Mechanistic Model","content":"\u003cp\u003eThe model is structured around the three conceptually distinct levels introduced in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The free energy of peptide assemblies can be conceptually decomposed as:\u003c/p\u003e\n\u003ch3\u003eG_int = G_HB + G_hydrophobic + G_steric + G_solvation + G_surface\u003c/h3\u003e\n\u003cp\u003eFor Level 1 (homochiral vs. racemic), the comparison involves primarily G_HB, G_steric, and G_solvation [\u003cspan additionalcitationids=\"CR45 CR46\" citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e]. For Level 2 (L vs. D), G_surface introduces a direction-dependent contribution from chiral mineral surface contacts [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e].\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eNucleation kinetics\u003c/h2\u003e \u003cp\u003eFrom transition-state theory, the nucleation rate constant depends exponentially on the free-energy barrier [\u003cspan additionalcitationids=\"CR49\" citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e]:\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003ek\u0026thinsp;=\u0026thinsp;k₀ exp(\u0026ndash;ΔG\u0026Dagger; / RT)\u003c/h2\u003e \u003cp\u003eIf, at a specific chiral mineral surface site, an L-type homochiral nucleus has a slightly lower activation barrier than a D-type nucleus:\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003ek_L / k_D\u0026thinsp;=\u0026thinsp;exp(\u0026ndash;(ΔG\u0026Dagger;_L \u0026ndash; ΔG\u0026Dagger;_D) / RT)\u003c/h2\u003e \u003cp\u003eThis exponential dependence converts small energetic differences into potentially significant rate differences.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eConnection to autocatalytic amplification\u003c/h2\u003e \u003cp\u003eMineral-mediated selection alone may be insufficient to produce macroscopic homochirality, because different surface sites may favor different enantiomers and the per-site bias may be small. The autocatalytic amplification framework of Ghadiri and colleagues [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] provides the necessary positive feedback: once any local environment achieves sufficient enantiomeric excess, chiroselective self-replication can lock in and amplify that excess. Mineral-mediated directional selection and autocatalytic amplification are thus complementary: the former provides the initial directional seed, the latter amplifies it.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eMineral Lattice Compatibility\u003c/h2\u003e \u003cp\u003eThe ~\u0026thinsp;4.7 \u0026Aring; inter-strand spacing of cross-β structures is robust across diverse peptide sequences [\u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Several candidate minerals exhibit surface lattice periodicities in a comparable range (Supplementary Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e). However, the comparison requires qualification: surface periodicities depend on the specific crystal face exposed, surface reconstruction can alter effective spacings, and no surface characterization of greigite in aqueous environments has been reported. The broad range of 4\u0026ndash;6 \u0026Aring; cited for mineral spacings encompasses both well-matched and poorly matched values. Furthermore, in aqueous solution, intervening water layers may partially transmit or completely attenuate the geometric influence of the underlying lattice. Whether the mineral lattice periodicity is \u0026lsquo;felt\u0026rsquo; by an adsorbed peptide assembly through intervening water layers is an open question.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eQuantitative Analysis: Required Energetic Bias and Experimental Measurement Thresholds\u003c/h2\u003e \u003cp\u003eA key quantitative question for the present model is: what minimum activation free-energy difference |ΔΔG\u0026Dagger;| is required to achieve biologically relevant chiral enrichment within the available geological time, and is this difference within reach of current or foreseeable experimental and computational methods? \u003cb\u003eThis analysis provides specific targets for future experimental validation.\u003c/b\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eDerivation of the required energetic bias\u003c/h2\u003e \u003cp\u003eConsider a system of peptide assemblies undergoing repeated nucleation\u0026ndash;dissolution cycles at chiral mineral surfaces. Let α\u0026thinsp;=\u0026thinsp;k_L/k_D be the per-cycle enrichment factor. After N_eff effective cycles:\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003e(L/D)_final = (L/D)₀ \u0026times; α^N_eff\u003c/h2\u003e \u003cp\u003ewhere N_eff\u0026thinsp;=\u0026thinsp;η\u0026thinsp;\u0026times;\u0026thinsp;N is the effective number of selection cycles, N is the total number of physical cycles, and η is an efficiency factor (0\u0026thinsp;\u0026lt;\u0026thinsp;η\u0026thinsp;\u0026le;\u0026thinsp;1) that accounts for environmental noise, sign reversal between L-selecting and D-selecting surface sites, dilution, hydrolysis, racemization, and competing reactions. The efficiency factor η is the most uncertain parameter in the model and is likely to be very small in realistic prebiotic environments.\u003c/p\u003e \u003cp\u003eSetting (L/D)_final to the target enrichment and solving for the required per-cycle bias ε\u0026thinsp;=\u0026thinsp;α \u0026ndash; 1:\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003eε\u0026thinsp;=\u0026thinsp;ln(target) / N_eff\u003c/h2\u003e \u003cp\u003eFrom transition-state theory, the corresponding activation free-energy difference is:\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec20\" class=\"Section2\"\u003e \u003ch2\u003e|ΔΔG\u0026Dagger;| = ε\u0026thinsp;\u0026times;\u0026thinsp;RT\u003c/h2\u003e \u003cdiv id=\"Sec21\" class=\"Section3\"\u003e \u003ch2\u003eParameter space analysis\u003c/h2\u003e \u003cp\u003eFigure 4 maps the required |\u0026Delta;\u0026Delta;G\u0026Dagger;| as a function of the efficiency factor \u0026eta; for three representative cycling frequencies (1-hour, 1-day, and 1-year intervals), with T = 333 K (60\u0026deg;C, representative of warm hydrothermal environments [51,52]), available geological time = 5 \u0026times; 10⁸ years (from Earth formation to the earliest evidence of life), and target L/D = 10⁶ (effective homochirality).\u003c/p\u003e\u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec22\" class=\"Section2\"\u003e \u003ch2\u003eInterpretation and experimental implications\u003c/h2\u003e \u003cp\u003eSeveral conclusions emerge from this analysis:\u003c/p\u003e \u003cp\u003e \u003cem\u003e(1) The theoretical minimum bias is extraordinarily small.\u003c/em\u003e For optimistic to moderate scenarios (η\u0026thinsp;=\u0026thinsp;10⁻\u0026sup1; to 10⁻\u0026sup2;), the required |ΔΔG\u0026Dagger;| is 10⁻⁷ to 10⁻⁵ kJ/mol\u0026mdash;many orders of magnitude below thermal noise (RT\u0026thinsp;\u0026asymp;\u0026thinsp;2.77 kJ/mol at 333 K). This demonstrates that the energetic threshold is not the limiting factor; rather, the critical question is whether a net directional bias survives environmental averaging.\u003c/p\u003e \u003cp\u003e \u003cem\u003e(2) Conservative scenarios approach experimental limits.\u003c/em\u003e For η\u0026thinsp;=\u0026thinsp;10⁻⁴ with daily cycling, the required |ΔΔG\u0026Dagger;| is approximately 10⁻\u0026sup2; to 10⁻\u0026sup1; kJ/mol, which overlaps with the precision of state-of-the-art computational chemistry methods (DFT/MD). This suggests that molecular dynamics simulations of peptide adsorption on well-defined chiral mineral surfaces could provide a meaningful test of the hypothesis.\u003c/p\u003e \u003cp\u003e \u003cem\u003e(3) Pessimistic scenarios require larger biases.\u003c/em\u003e For η\u0026thinsp;=\u0026thinsp;10⁻⁶ with annual cycling, the required |ΔΔG\u0026Dagger;| reaches 10\u0026deg; to 10\u0026sup1; kJ/mol, well within the range of experimental calorimetry. In this regime, direct experimental measurement of enantioselective adsorption energetics on iron\u0026ndash;sulfur mineral surfaces would provide a definitive test.\u003c/p\u003e \u003cp\u003eImportantly, the measured enantiospecific binding energy difference for aspartic acid on calcite (~\u0026thinsp;33 kJ/mol [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]) is orders of magnitude larger than the required |ΔΔG\u0026Dagger;| in any scenario except the most pessimistic. This indicates that mineral surface enantioselectivity of the required magnitude is physically achievable\u0026mdash;though the relevant quantity for the present model is the much smaller difference in nucleation barriers for supramolecular assemblies, not individual molecular binding energies.\u003c/p\u003e \u003cdiv id=\"Sec23\" class=\"Section3\"\u003e \u003ch2\u003eLimitations of the α^N_eff calculation\u003c/h2\u003e \u003cp\u003eThis analysis rests on three idealizations: (i) that each cycle produces a directional bias of the same sign, whereas in reality different surface sites may favor different enantiomers; (ii) that there are no back-reactions, dilution, or loss between cycles; (iii) that environmental noise does not overwhelm the signal. The efficiency factor η is introduced to account for these effects in an aggregate way, but its value is unknown and may itself vary over orders of magnitude depending on environmental conditions. We therefore present this analysis not as a quantitative prediction, but as a framework for identifying the experimental measurements needed to test the hypothesis.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cdiv id=\"Sec25\" class=\"Section2\"\u003e \u003ch2\u003eWhat the model claims and does not claim\u003c/h2\u003e \u003cp\u003e \u003cstrong\u003eEstablished\u003c/strong\u003e \u003cp\u003e(a) Chiral mineral surface features exist and can enantioselectively adsorb amino acids (demonstrated for calcite [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]). (b) Peptides self-assemble into β-sheet structures with ~\u0026thinsp;4.7 \u0026Aring; periodicity [\u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. (c) Homochiral peptide assemblies are generally more ordered than racemic mixtures [\u003cspan additionalcitationids=\"CR54\" citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e]. (d) Autocatalytic peptide replicators can amplify existing enantiomeric excesses [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eProposed but not yet tested\u003c/strong\u003e \u003cp\u003e(a) Iron\u0026ndash;sulfur mineral surfaces present chiral features capable of enantioselective interactions with peptides. (b) β-sheet nucleation kinetics are measurably influenced by chiral mineral surface geometry. (c) The geometric match between β-sheet periodicity and mineral surface spacing is functionally significant in aqueous environments.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eBeyond scope\u003c/strong\u003e \u003cp\u003e(a) How local chiral enrichment was propagated to planetary-scale homochirality. (b) The specific geological scenario that produced a net L-bias.\u003c/p\u003e \u003c/p\u003e \u003cdiv id=\"Sec26\" class=\"Section3\"\u003e \u003ch2\u003eStrengths\u003c/h2\u003e \u003cp\u003eThe model integrates independently established physical phenomena into a coherent framework that identifies a specific physical mechanism for directional chiral selection\u0026mdash;a gap in existing theories. The energetic requirements are modest, and the parameter space analysis (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e) provides concrete experimental targets. The model is compatible with the autocatalytic amplification framework [\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] and generates testable predictions distinguishable from universal-asymmetry models [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec27\" class=\"Section3\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eThe most significant limitation is the absence of direct experimental evidence for the central hypothesis: enantioselective peptide β-sheet nucleation on iron\u0026ndash;sulfur mineral surfaces. The local-to-global propagation problem remains unresolved. The role of Mg\u0026sup2;⁺ and structured interfacial water, while conceptually attractive, remains speculative. The idealized amplification calculation overstates effective enrichment by neglecting environmental noise and spatial heterogeneity.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec28\" class=\"Section2\"\u003e \u003ch2\u003eExperimental testability\u003c/h2\u003e \u003cp\u003eThe parameter space analysis (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e) suggests a prioritized experimental program:\u003c/p\u003e \u003cp\u003e \u003cstrong\u003e(1) Enantioselective amino acid adsorption on iron\u0026ndash;sulfur minerals\u003c/strong\u003e \u003cp\u003eRepeating Hazen\u0026rsquo;s calcite experiments [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e] with greigite, mackinawite, or pyrite would directly test the key assumption.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003e(2) Molecular dynamics simulations\u003c/strong\u003e \u003cp\u003eDFT/MD calculations of peptide adsorption on hydrated iron\u0026ndash;sulfur surfaces could estimate enantiospecific binding energies and nucleation barriers. Figure\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e indicates that computational precision of ~\u0026thinsp;0.01 kJ/mol would be informative for moderate-efficiency scenarios.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003e(3) Peptide nucleation kinetics on chiral mineral surfaces\u003c/strong\u003e \u003cp\u003eUsing quartz crystal microbalance, AFM, or surface-sensitive spectroscopy to compare L- vs. D-peptide aggregation kinetics on chiral crystal faces [\u003cspan additionalcitationids=\"CR57\" citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e].\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003e(4) Cyclic enrichment experiments\u003c/strong\u003e \u003cp\u003eMicrofluidic wet\u0026ndash;dry cycling reactors to test whether repeated assembly\u0026ndash;disassembly cycles on chiral mineral surfaces produce measurable enantiomeric enrichment [\u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e].\u003c/p\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec29\" class=\"Section2\"\u003e \u003ch2\u003eAstrobiological implications\u003c/h2\u003e \u003cp\u003eIf mineral-surface-mediated directional selection operates as proposed, biological homochirality reflects contingent planetary geochemistry in its specific direction. Discovery of D-amino acid-based life on another planet would support contingent selection mechanisms. The model predicts that homochirality is a predictable consequence of generic geochemical processes, even though its specific direction would vary by planet.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eWe have presented a conceptual model proposing that chiral mineral\u0026ndash;seawater interfaces could have contributed to the initial directional selection of amino acid chirality. The model addresses a specific gap in existing theories: the origin of directional chiral bias. We emphasize the distinction between three levels of the problem (homochiral vs. racemic; L vs. D direction; local vs. global) and contribute primarily to the second.\u003c/p\u003e \u003cp\u003eThe quantitative parameter space analysis provides specific experimental targets: for realistic efficiency factors, the required energetic biases range from computationally accessible (~\u0026thinsp;0.01 kJ/mol) to experimentally measurable (~\u0026thinsp;0.1 kJ/mol), depending on the assumed environmental noise and cycling frequency. The known enantiospecific binding energy on calcite (~\u0026thinsp;33 kJ/mol) far exceeds these thresholds, establishing the physical plausibility of the mechanism.\u003c/p\u003e \u003cp\u003eThe most significant limitation remains the absence of direct experimental evidence for enantioselective peptide nucleation on iron\u0026ndash;sulfur mineral surfaces. We have outlined a prioritized experimental program to test the model\u0026rsquo;s key predictions, guided by the parameter space analysis of Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eCompeting Interests\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe author declares no competing financial or non-financial interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eFunding\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research received no specific funding from any agency in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAuthor Contributions\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eM. Miyake is the sole author and is responsible for all aspects of this work, including conceptualization, theoretical development, quantitative analysis, and manuscript preparation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eUse of AI Tools\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn accordance with Springer Nature\u0026rsquo;s policy on the use of large language models (LLMs), the author discloses that an AI assistant (Anthropic Claude, Claude Opus 4) was used during manuscript preparation. The AI tool was used for the following purposes: assistance with literature search and organization, structural and organizational suggestions for manuscript drafting, verification of mathematical expressions, generation of figure drafts, and English language editing. All scientific hypotheses, intellectual content, theoretical reasoning, and interpretive conclusions are solely those of the author. The AI tool does not meet the journal\u0026rsquo;s criteria for authorship, as it cannot take accountability for the work, and is therefore not listed as an author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eData Availability\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis is a theoretical/conceptual paper. No experimental data were generated. All parameters used in the quantitative analysis are stated explicitly in the text and figures.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eEthics, Consent to Participate, and Consent to Publish\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eClinical Trial Number\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMiller SL (1953) A production of amino acids under possible primitive Earth conditions. Science 117:528\u0026ndash;529\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMiller SL, Urey HC (1959) Organic compound synthesis on the primitive Earth. 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Angew Chem Int Ed 54:9871\u0026ndash;9875\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Homochirality, amino acid chirality, mineral surface, peptide self-assembly, β-sheet nucleation, prebiotic chemistry, origin of life","lastPublishedDoi":"10.21203/rs.3.rs-9392776/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9392776/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe origin of biological homochirality\u0026mdash;the near-exclusive use of L-amino acids in proteins\u0026mdash;remains one of the most persistent unsolved problems in studies of life\u0026rsquo;s emergence. Here we present a conceptual geochemical model in which peptide β-sheet self-assembly at chiral mineral\u0026ndash;seawater interfaces could generate directional kinetic selection of chirality. We propose that this mechanism may have contributed to the initial enantiomeric bias that preceded, and was subsequently amplified by, autocatalytic and evolutionary processes.\u003c/p\u003e \u003cp\u003eWe distinguish three conceptually distinct levels of the homochirality problem: (i) the preference for homochiral over racemic assemblies; (ii) the directional selection of a specific enantiomer (L vs. D) at individual mineral surface sites; and (iii) the propagation of local enrichment to planetary-scale homochirality. The present work focuses on level (ii), proposing chiral mineral surface structures as a candidate source of directional bias, while acknowledging that levels (i) and (iii) involve additional mechanisms.\u003c/p\u003e \u003cp\u003eβ-sheet assemblies are selected as the focus because their characteristic interstrand spacing (~\u0026thinsp;4.7 \u0026Aring;, as measured by X-ray diffraction of cross-β structures) faces the mineral surface directly, enabling potential two-dimensional geometric templating\u0026mdash;a mode of interaction geometrically less accessible for α-helices. Several minerals abundant on the early Earth present surface lattice periodicities in a broadly comparable range. Crucially, mineral crystal faces can present intrinsically chiral surface structures that interact enantioselectively with adsorbed amino acids, as demonstrated experimentally for calcite. We hypothesize that analogous chiral surface features on iron\u0026ndash;sulfur minerals, combined with asymmetric coordination environments involving hydrated Mg\u0026sup2;⁺ ions, could create conditions favoring one enantiomer during peptide nucleation.\u003c/p\u003e \u003cp\u003eWe derive the minimum activation free-energy difference |ΔΔG\u0026Dagger;| required to achieve biologically relevant chiral enrichment as a function of environmental parameters, and map this against current experimental and computational measurement thresholds. This analysis provides specific quantitative targets for future experimental validation. We emphasize that the model remains at a conceptual stage: direct evidence for enantioselective peptide nucleation on iron\u0026ndash;sulfur minerals is not yet available, and the propagation of local enrichment to global homochirality remains an open problem.\u003c/p\u003e","manuscriptTitle":"Toward a Geochemical Model for Directional Chiral Selection: Peptide β-Sheet Nucleation at Chiral Mineral–Seawater Interfaces as a Candidate Mechanism","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-29 09:33:02","doi":"10.21203/rs.3.rs-9392776/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3a0c88b8-3121-4163-be6c-c799d7dc8343","owner":[],"postedDate":"April 29th, 2026","published":true,"recentEditorialEvents":[{"type":"editorInvited","content":"","date":"2026-05-04T09:36:01+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-04-29T09:33:02+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-29 09:33:02","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9392776","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9392776","identity":"rs-9392776","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}