Programming Biomimetic Self-Assembly through Solvent-Encoded Pathway Selection

Programming Biomimetic Self-Assembly through Solvent-Encoded Pathway Selection | 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 Article Programming Biomimetic Self-Assembly through Solvent-Encoded Pathway Selection Song Yang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9380005/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Supramolecular self-assembly has evolved from the characterization of static structures toward the dynamic regulation of assembly pathways. Although solvent environment plays a key role in this evolution by modulating noncovalent interactions, the molecular-level mechanisms through which solvation governs pathway selection remain scarce. Here, we use Fmoc-cystine (FC) as a model building block to establish a solvent biomimetic environmental encoding strategy for regulating self-assembly pathways and multiscale nanostructures. By integrating Hansen solubility parameters with external energy inputs and concentration gradients, we develop a systematic framework to investigate solvent-directed assembly behavior. Combining comprehensive analysis of TEM, 1 H NMR, FT-IR, XRD, fluorescence and theoretical results, we successfully disclose the hydrogen bonding templates primary fibrous structures, π-π stacking directs molecular alignment and bundling, and electrostatic interactions mediate macroscopic phase transitions without altering nanoscale morphology. Moreover, leveraging the intrinsic redox-responsive disulfide bonds of FC, we develop a supramolecular platform featuring reversible assembly disassembly and dual-compartment drug loading, enabling targeted delivery and functional imaging. This work offers a generalizable strategy for the rational design of dynamically adaptive functional materials with potential applications in biomedicine. Physical sciences/Materials science/Nanoscale materials Physical sciences/Materials science/Nanoscale materials/Molecular self-assembly Self-assembly Fmoc-cystine Hansen solubility parameters Supramolecular platform Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SIProgrammingBiomimeticSelfAssemblythroughSolventEncodedPathwaySelection1.docx Programming Biomimetic Self-Assembly through Solvent-Encoded Pathway Selection Cite Share Download PDF Status: Under Review 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-9380005","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":628215035,"identity":"76f5b69a-502d-4f0d-8e6e-11f0a79b8806","order_by":0,"name":"Song Yang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAy0lEQVRIiWNgGAWjYBACxhlQBj+ISCggRYtkA0iLATHWSEBpgwNgkggdzLPbn0kw5tRFG59fnfjhgQGDPL/YAQIOm3Mg2YBx2+HcbTfebpYAOsxw5uwEAlpmJBx8wLjtAFDL2Q0gLQkGtwlqSWw4wLitLnfzjLObfxCpJZkRaAtz7gb+3m3E2pLGbJAI9MuMG7zbLBIMJAj7xXBG+jOJj0CH9fef3XzzR4WNPL80IS0NQAKsRgJC4lcOAvJwFv8BwqpHwSgYBaNgZAIAwGhHOy1gt8AAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0003-1301-3030","institution":"Guizhou University","correspondingAuthor":true,"prefix":"","firstName":"Song","middleName":"","lastName":"Yang","suffix":""}],"badges":[],"createdAt":"2026-04-10 13:20:44","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9380005/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9380005/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":107707776,"identity":"ef13db9f-9b2a-4204-b7f0-cd079dd4d0fd","added_by":"auto","created_at":"2026-04-24 09:21:08","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1590139,"visible":true,"origin":"","legend":"","description":"","filename":"ManuscriptProgrammingBiomimeticSelfAssemblythroughSolventEncodedPathwaySelection2.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9380005/v1_covered_715dd3f1-0859-4ee1-a05c-834870ffbc2a.pdf"},{"id":107694618,"identity":"c91b91d2-01bd-47ed-9508-147041ec1fae","added_by":"auto","created_at":"2026-04-24 06:48:02","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":8685055,"visible":true,"origin":"","legend":"Programming Biomimetic Self-Assembly through Solvent-Encoded Pathway Selection","description":"","filename":"SIProgrammingBiomimeticSelfAssemblythroughSolventEncodedPathwaySelection1.docx","url":"https://assets-eu.researchsquare.com/files/rs-9380005/v1/e9cf5597c0af64338fdfe6b5.docx"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"Programming Biomimetic Self-Assembly through Solvent-Encoded Pathway Selection","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"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":"Self-assembly, Fmoc-cystine, Hansen solubility parameters, Supramolecular platform","lastPublishedDoi":"10.21203/rs.3.rs-9380005/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9380005/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eSupramolecular self-assembly has evolved from the characterization of static structures toward the dynamic regulation of assembly pathways. 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