Concentration-dependent modes of melittin-induced membrane destabilization: an integration of experimental and computational tools

Concentration-dependent modes of melittin-induced membrane destabilization: an integration of experimental and computational tools | Research Square 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 Help Center Sign In Submit a Preprint Cite Share Download PDF Article Concentration-dependent modes of melittin-induced membrane destabilization: an integration of experimental and computational tools Ildefonso Marin-Montesinos, Andrea Chacón Calderón, Pavel Zelenovskii, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8935745/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 Melittin is a well-known antimicrobial peptide whose mechanism of action is still not entirely understood. In this study, we combine complementary experimental techniques with molecular dynamics simulations to determine melittin-membrane interactions at different scales. Using 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE):1,2-dipalmitoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (DPPG) membranes that mimic the Escherichia coli inner membrane, this integrative approach reveals a clear transition in melittin’s mode of action with increasing loading. At low concentrations, melittin primarily perturbs the membrane interface, inducing modest surface expansion and subtle lipid reorganization. At higher concentrations, the membrane response shifts toward increased hydration, lipid disorder, membrane thinning, and morphological remodeling. Simulations support these observations, linking concentration-dependent membrane responses to enhanced lipid mobility and stronger effects on anionic DPPG. Melittin, therefore, affects the membrane in a concentration dependent-manner, transitioning from surface-bound carpet-like permeabilization at low loading to transient pore formation and membrane reorganization at higher concentrations. Biological sciences/Chemical biology/Membranes Biological sciences/Chemical biology/Lipids/Membrane lipids Biological sciences/Chemical biology/Peptides Biological sciences/Chemical biology/Mechanism of action Biological sciences/Chemical biology/Chemical tools Full Text Additional Declarations There is NO Competing Interest. Supplementary Files AMPmembranesSupportingInformation2.docx Supporting Information Concentration-dependent modes of melittin-induced membrane destabilization: an integration of experimental and computational tools 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 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

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