Trans-bilayer asymmetry of anoplin binding governs phase transitions in mixed model membranes.

Authors

Vedrana Krajnović, Bence Fehér, Andreja Jakas, Jan Stránský, Danijela Bakarić

Published in

Journal of liposome research. Pages 1-12. Nov 01, 2026. Epub Nov 01, 2026.

Abstract

Antimicrobial peptides are promising alternatives to conventional antibiotics due to their membrane-disrupting capabilities. Here, we investigated the action of anoplin (ANP), a cationic-amphipathic decapeptide, on model bacterial membranes composed of zwitterionic 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) or 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE) and anionic 1,2-dipalmitoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (DPPG) (3/1 molar ratio). Using differential scanning calorimetry (DSC), turbidity measurements (UV-Vis spectroscopy), and circular dichroism (CD) spectroscopy, we examined how zwitterionic headgroup chemistry and leaflet distribution asymmetry - external adherence (ANPout) versus both internal and external adherence (ANPin/out) - modulate lipid segregation and membrane thermotropic properties before leakage. In DPPC/DPPG bilayers, ANP positioning governed membrane viscoelasticity: ANPout made the bilayer more fluid, whereas ANPin/out increased membrane rigidity. In contrast, in DPPE/DPPG bilayers, the promoted DPPG segregation was largely independent of ANP distribution. Importantly, cooperativity signatures changed in both mixtures: in the DPPC-containing mixture, they differ for the ANPout system, whereas in all DPPE-containing mixtures they do not display a common sigmoidal profile. CD spectroscopy revealed that ANP maintains a helical conformation in DPPC/DPPG across both gel and fluid phases, whereas DPPE/DPPG fosters β-sheet-rich peptide aggregation. Coupled with the intrinsic negative curvature of DPPE, this enhanced aggregation likely induces membrane corrugations at the surface that obscure the obtained turbidity profiles. Besides demonstrating that zwitterionic lipid modulates ANP's secondary structure and domain segregation, the ANP distribution along the membrane midplane critically regulates bilayer mechanical properties. This highlights leaflet-specific inter-lipid interactions and peptide translocation as pivotal factors driving ANP-mediated membrane disruption and permeabilization.

PMID:
42967308
Bibliographic data and abstract were imported from PubMed on 02 Nov 2026.

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