Coarse-grained molecular dynamics of membrane semitoroidal pore formation in model lipid-peptide systems

Abstract Transmembrane pores play an important role in various cell processes. However, the detailed structures of these pores and their influence on the membrane properties remain undetermined. We performed microsecond coarse-grained molecular dynamics simulations to study the interaction of cationic β-structural peptides with multicomponent lipid bilayers consisting of two types of anionic (POPS, POPI) and two types of zwitterionic (POPE, POPC) lipids. The formation of semitoroidal pores was analyzed from a standpoint of self-organization of lipids and peptides. Our results showed that semitoroidal pores were mainly formed by POPI molecules with a strong negative charge. We found that peptide aggregation is a necessary step of pore formation; single peptide is unable to stabilize the semitoroidal pore. To characterize the influence of semitoroidal pores on membrane properties, we evaluated the bilayer thickness, the two-dimensional density maps of lipids, the deuterium order parameters, and the lateral diffusion coefficients of lipids. The pore formation induced perturbation of the phospholipid organization in membrane and facilitated the organization of zones with different electrostatic potential.