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

Sergey A Akimov,Peter I Kuzmin,Timur R Galimzyanov,Konstantin V Pavlov,Oleg V Batishchev,Pavel E Volynsky

doi:10.1038/s41598-017-12127-7

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.

Highlights

Lipid bilayer constitutes a major structural component of plasma membranes[1]
In refs[12,13], pores were postulated to evolve from membrane hydrophobic defects in the form of water-filled hydrophobic cylinders occurring through lateral displacements of lipid molecules
We have developed a model of hydrophilic pore formation from an intact bilayer through a hydrophobic defect

Summary

Introduction

Lipid bilayer constitutes a major structural component of plasma membranes[1]. Amphiphilic nature of lipid molecules, which contain both polar and hydrophobic parts, determines low permeability of lipid bilayers for broad range of substances and allows the membranes to perform barrier function effectively in the cells. The surface of the hydrophilic pore was assumed torus-shaped[14], with only bending deformations of the membrane taken into account This is equivalent to potentially unlimited amount of energy being tacitly added to the system to maintain the postulated shape. Under these conditions, line tension is a non-monotonous function of the pore radius. Toroidal shape of the pore boundary surface postulated in ref.[14] yields the line tension values notably (by a factor of 2–3) exceeding the experimental values. A model of pore boundary structure yielding the line tension values consistent with the experimental results was proposed in the work ref.[15]. As we have previously demonstrated, breaking the pore boundary down to as few as three parts is sufficient in the sense that further breakdown does not cause the calculated pore boundary energy to decrease[8]

Methods

Results

Discussion

Conclusion