Pore formation in lipid membrane I: Continuous reversible trajectory from intact bilayer through hydrophobic defect to transversal pore

Abstract

Lipid membranes serve as effective barriers allowing cells to maintain internal composition differing from that of extracellular medium. Membrane permeation, both natural and artificial, can take place via appearance of transversal pores. The rearrangements of lipids leading to pore formation in the intact membrane are not yet understood in details. We applied continuum elasticity theory to obtain continuous trajectory of pore formation and closure, and analyzed molecular dynamics trajectories of pre-formed pore reseal. We hypothesized that a transversal pore is preceded by a hydrophobic defect: intermediate structure spanning through the membrane, the side walls of which are partially aligned by lipid tails. This prediction was confirmed by our molecular dynamics simulations. Conversion of the hydrophobic defect into the hydrophilic pore required surmounting some energy barrier. A metastable state was found for the hydrophilic pore at the radius of a few nanometers. The dependence of the energy on radius was approximately quadratic for hydrophobic defect and small hydrophilic pore, while for large radii it depended on the radius linearly. The pore energy related to its perimeter, line tension, thus depends of the pore radius. Calculated values of the line tension for large pores were in quantitative agreement with available experimental data.

Elastic deformations mediate interaction of the raft boundary with membrane inclusions leading to their effective lateral sorting

“…5A-C). Typically, a local increase in the concentration of lipids having a positive spontaneous curvature leads to the formation of through pores in membranes 45 , even in the presence of cholesterol 51,77 , which has a highly negative spontaneous curvature 78,79 . However, the enrichment of ganglioside GM1 at the domain boundary is not accompanied by the pore formation 27,31 , while the enrichment of lysolipids produced by phospholipase A2 indeed results in the membrane poration 77 .…”

“…Besides, GM1 has a large polar part in comparison with lysophosphatidylcholines. Large polar heads may hinder GM1 molecules reorientation, which is an essential stage of the hydrophilic pore formation 45,46 .…”

“…To explain the mechanism of the line activity, a concept of so-called hybrid lipids was proposed 28 : in order to be line-active, hybrid lipids www.nature.com/scientificreports www.nature.com/scientificreports/ calculated up to the second order in deformations, which are assumed to be small. In a quadratic approximation, the elastic energy of the monolayer can be expressed as 40,45,46 : Scientific RepoRtS | (2020) 10:4087 | https://doi.…”

Switching between Successful and Dead-End Intermediates in Membrane Fusion

“…For each of the scenarios, we calculate the total energy of the system consisting of the two membranes. In order to calculate the deformational component of the energy, we employ an adaptation of the liquid crystal elasticity theory to lipid membranes (for detailed description of the methodology see, e.g., [ 43 , 44 , 45 ]). The membrane is treated as a continuous medium subject to elastic deformations.…”

Membrane pore energetics and the pathways to membrane rupture

“…An earlier study of black lipid membrane (BLM) electroporation similarly suggested that pore opening kinetics involved metastable pre-pore defect states with extremely long lifetimes 0.1-1 s (26). The possibility of metastable pre-pore states was suggested by other theoretical models and atomistic simulations (12,27,28).…”