Dose-Dependent Softening of Bacterial Model Membranes by Structurally Distinct Antimicrobial Peptides: A Coarse-Grained Molecular Dynamics Study

Authors

Saiba, R., Baratam, K., Chakraborty, D., Vemparala, S.

Abstract

Antimicrobial peptides (AMPs) act at the membrane interface, where they remodel lipid packing defects and redistribute lateral stresses, yet a quantitative, dose-dependent understanding of how they alter membrane mechanical properties remains incomplete. We use coarse-grained MARTINI 3 molecular dynamics simulations to systematically characterize the mechanical and microstructural response of a 70:30 POPE:POPG bilayer to three AMPs spanning distinct structural classes: aedesin (alpha-helical, 2MMM), arenicin-1 (beta-hairpin, 2JSB), and indolicidin (disordered, 1G89). For each peptide we vary the surface loading from one to four peptides per leaflet and extract the bending modulus $K_c$, the area compressibility modulus $K_A$, peptide localization depth, bilayer thickness, peptide-lipid and peptide-peptide spatial organization, and leaflet-resolved lipid packing defect distributions. All three peptides soften $K_c$ monotonically with loading, but at per-peptide rates that span a threefold range and order systematically by structural class: $-1.39 pm 0.09$, $-0.66 pm 0.04$, and $-0.44 pm 0.01$ kbt per peptide for aedesin, arenicin-1, and indolicidin, respectively. The tilt and twist moduli remain invariant across all conditions, indicating that the perturbation operates selectively on long-wavelength collective deformation modes. $K_A$ softens for the two structured peptides but is statistically indistinguishable from the control for indolicidin, a dissociation we trace to a supraphosphate adsorption versus interfacial insertion dichotomy: structured peptides sit above the phosphate plane and act as supraphosphate wedges, while the disordered peptide threads into the interface without coherently displacing lipids. Independent geometric, spatial-organization, and microstructural observables corroborate this framework, with the deep versus shallow defect remodeling asymmetry providing a clean microstructural counterpart to the $K_c$--$K_A$ dichotomy. Acyl chain order parameters resolve the per-lipid splay from the bilayer-averaged response and show that the per-lipid perturbation tracks conformational state rather than peptide length: the two structured peptides impose comparable per-lipid chain disordering despite differing in length, while the disordered peptide imposes far less. These findings establish a quantitative connection between peptide-induced defect remodeling and the elastic response of the bilayer, and suggest a design principle in which conformational restriction maximizes the per-peptide membrane perturbation, motivating experimental tests on stapled-peptide AMP analogs.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 22 Jun 2026.

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