{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T06:18:10Z","timestamp":1788589090772,"version":"build-2803163510"},"reference-count":55,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T00:00:00Z","timestamp":1764720000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Membranes"],"abstract":"<jats:p>The cell-penetrating peptide Pep-1 interacts with lipid membranes through combined electrostatic and hydrophobic forces, yet the structural details of its membrane remodeling activity remain unclear. Using atomic force microscopy (AFM), we examined how Pep-1 perturbs supported lipid bilayers of varying composition and geometry. In zwitterionic POPC bilayer patches, Pep-1 preferentially targeted patch boundaries, where lipid packing is less constrained, leading to edge erosion and detergent-like disintegration. Incorporation of anionic POPS enhanced peptide binding and localized disruption, giving rise to elevated annular rims, holes, and peptide\u2013lipid aggregates. In cholesterol-containing POPC bilayer patches, Pep-1 induced extensive surface reorganization marked by protruded, ridge-like features, consistent with lipid redistribution and curvature generation. In continuous POPC\/POPS bilayers lacking free edges, Pep-1 formed discrete, flower-like protrusions that coalesced into an interconnected network of thickened peptide-rich domains. These findings reveal composition-dependent remodeling pathways in which Pep-1 destabilizes, reorganizes, or curves membranes according to their mechanical and electrostatic properties, providing new insight into peptide\u2013membrane interactions relevant to cell-penetrating peptide translocation.<\/jats:p>","DOI":"10.3390\/membranes15120373","type":"journal-article","created":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T11:29:30Z","timestamp":1764761370000},"page":"373","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Curvature-Induced Membrane Remodeling by the Cell-Penetrating Peptide Pep-1"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-9683-6209","authenticated-orcid":false,"given":"Yasith Indigahawela","family":"Gamage","sequence":"first","affiliation":[{"name":"Department of Physics, University of South Florida, Tampa, FL 33620, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianjun","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Physics, University of South Florida, Tampa, FL 33620, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1016\/0092-8674(88)90263-2","article-title":"Cellular Uptake of the Tat Protein from Human Immunodeficiency Virus","volume":"55","author":"Frankel","year":"1988","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1016\/0092-8674(88)90262-0","article-title":"Autonomous Functional Domains of Chemically Synthesized Human Immunodeficiency Virus Tat Trans-Activator Protein","volume":"55","author":"Green","year":"1988","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1864","DOI":"10.1073\/pnas.88.5.1864","article-title":"Antennapedia homeobox peptide regulates neural morphogenesis","volume":"88","author":"Joliot","year":"1991","journal-title":"Proc. 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