RT Journal Article T1 Antimicrobial peptides at (lipid) interfaces: Insights from monolayer models A1 Antelo Riveiro, Paula A1 García Fandiño, Rebeca A1 Piñeiro Guillén, Ángel K1 Antimicrobial peptides K1 Lipid interfaces K1 Peptide-lipid interactions K1 Interfacial thermodynamics K1 Langmuir monolayers K1 Molecular modeling AB 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 advantagesand 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. PB Elsevier SN 0001-8686 YR 2026 FD 2026 LK https://hdl.handle.net/10347/46628 UL https://hdl.handle.net/10347/46628 LA eng NO Antelo‑Riveiro, P., García‑Fandiño, R., Piñeiro, Á. (2026). Antimicrobial peptides at (lipid) interfaces: Insights from monolayer models." Advances in Colloid and Interface Science", 350 NO This work was supported by the Spanish Agencia Estatal de Investigación (AEI) and the ERDF (PID2022-141534OB-I00 and CNS2023-144353), by Xunta de Galicia (ED431C 2025/15, ED431C 2021/21 and Centro de investigación do Sistema universitario de Galicia accreditation 2023-2027, ED431G 2023/03) and the European Union (European Regional Development Fund – ERDF). P.A-R. thanks Xunta de Galicia for her predoctoral contract (ED481A-2024-073). DS Minerva RD 22 may 2026