Antimicrobial peptides at (lipid) interfaces: Insights from monolayer models

Antimicrobial peptides (AMPs) are key effectors of innate immunity that, beyond their canonical activity, exhibit promising therapeutic potential against cancer and cellular senescence. Their efficacy relies on selective membrane disruption driven by specific lipid signatures, yet quantifying these...

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Detalles Bibliográficos
Autores: Antelo Riveiro, Paula, García Fandiño, Rebeca, Piñeiro Guillén, Ángel
Tipo de recurso: artículo
Fecha de publicación:2026
País:España
Institución:Universidad de Santiago de Compostela (USC)
Repositorio:Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
Idioma:inglés
OAI Identifier:oai:dnet:minerva_____::74c3c9fcd8f4bbae757b6e1031825d21
Acceso en línea:https://hdl.handle.net/10347/46628
Access Level:acceso abierto
Palabra clave:Antimicrobial peptides
Lipid interfaces
Peptide-lipid interactions
Interfacial thermodynamics
Langmuir monolayers
Molecular modeling
2306 Química orgánica
22 Física
Descripción
Sumario:Antimicrobial peptides (AMPs) are key effectors of innate immunity that, beyond their canonical activity, exhibit promising therapeutic potential against cancer and cellular senescence. Their efficacy relies on selective membrane disruption driven by specific lipid signatures, yet quantifying these interactions in complex bilayer systems remains challenging. Lipid monolayers serve as powerful reductionist models to isolate the physicochemical determinants of this selectivity, effectively mimicking the outer leaflet of bacterial, cancerous, or senescent membranes. This review provides a critical analysis of how lipid composition, packing density, and phase behavior modulate AMP adsorption and insertion. We systematically integrate thermodynamic profiling (surface pressure, compressibility, mixing energy) with advanced structural and morphological characterization. Special emphasis is placed on how spectroscopic techniques (IRRAS, GIXD, SFG) and real-time microscopy (BAM, fluorescence, AFM) resolve peptide orientation, secondary structure induction, and lipid domain remodeling at the mesoscale. These experimental observables are bridged with Molecular Dynamics (MD) simulations, establishing a feedback loop between macroscopic measurements and atomistic resolution. By defining the advantages and limitations of monolayer models relative to vesicles and bilayers, we outline a rational framework for leveraging interfacial insights in the design of next-generation peptide therapeutics and nanobiotechnological applications.