Spontaneous Buckling of Lipid Bilayer and Vesicle Budding Induced by Antimicrobial Peptide Magainin 2: A Coarse-Grained Simulation Study

Abstract

Molecular mechanisms of the action of antimicrobial peptides on bacterial membranes were studied by large scale coarse-grained simulations of magainin 2-dipalmitoylphosphatidylcholine/palmitoyloleoylphosphatidylglycerol (DPPC/POPG) mixed bilayer systems with spatial extents up to 0.1 μm containing up to 1600 peptides. Equilibrium simulations exhibit disordered toroidal pores stabilized by peptides. However, when a layer of peptides is placed near the lipid head groups on one side of the bilayer only, their incorporation leads to a spontaneous buckling of the bilayer. This buckling is followed by the formation of a quasi-spherical vesicular bud connected to the bilayer by a narrow neck. The mean curvature of the budding region is consistent with what is expected based on the dependence of the area per lipid on the peptide-to-lipid ratio in equilibrium simulations. Our simulations suggest that the incorporation of antimicrobial peptides on the exterior surface of a vesicle or a bacterial cell leads to buckling and vesicle budding, presumably accompanied by nucleations of giant transient pores of sizes that are much larger than indicated by equilibrium measurements and simulations.

LipidWrapper: An Algorithm for Generating Large-Scale Membrane Models of Arbitrary Geometry

“…As coarse-grained models contain fewer individual particles, they are widely used to simulate large-scale systems, including systems with large membrane components [61], [64], [65], [66], [67]. Simulations of these simplified models can access timescales on the order of milliseconds [68] and so are emerging as useful tools for studying lipid phase transitions [69], protein interactions with lipid bilayers [70], lipid budding [64], etc.…”

“…Simulations of these simplified models can access timescales on the order of milliseconds [68] and so are emerging as useful tools for studying lipid phase transitions [69], protein interactions with lipid bilayers [70], lipid budding [64], etc. If the initial planar bilayer model used as LipidWrapper input is itself coarse grained, LipidWrapper generates coarse-grained models directly.…”

Neutron Reflectivity as a Tool for Physics-Based Studies of Model Bacterial Membranes

“…This means that a model (or biomimetic) system must be used to facilitate such studies. One approach is to perform experiments in silico using molecular dynamics (MD) simulations at various levels of coarse-graining (Marrink et al 2009;Illya and Deserno 2008;Woo and Wallqvist 2011;Chen et al 2012). Such in silico experiments are attractive as it is possible to try things that are not necessarily feasible experimentally.…”

“…The importance of such elastic energy terms was demonstrated by a coarse-grained dissipative particle dynamics simulation of the interaction of the AMP maganin 2 with a bilayer composed of 4:1 DPPC/POPG by Woo and Wallqvist (2011). By using a large patch size (0.1 μm), they were able to suggest that the peptide induced disordered toroidal pores and that when the peptides are allowed to interact from only one side of the bilayer, they induce a buckling that produces a quasi-spherical bud connected by a narrow neck.…”

Entropic Forces Drive Clustering and Spatial Localization of Influenza A M2 During Viral Budding

“…In this work we systematically investigate the role of M2 in budding at a coarse-grained (CG) resolution using a combination of computer simulations and experiments. The use of theory and simulation to study fundamental processes has gained wide-spread popularity in the biophysical sciences, with CG models successfully applied to the investigation of processes related to viral budding such as vesicle budding by antimicrobial peptides (12), viral proteins and capsids (13)(14)(15), dynamin constriction (16), and nano-particle endocytosis (17)(18)(19). In our simulations, theoretical as well as experimental constraints are taken into account to ensure that the system studied presents a close correspondence with biological reality.…”