Biophysical Journal
Volume 106, Issue 1, 7 January 2014, Pages 210-219
Journal home page for Biophysical Journal

Article
Atomistic Simulations of Pore Formation and Closure in Lipid Bilayers

https://doi.org/10.1016/j.bpj.2013.11.4486Get rights and content
Under a Creative Commons license
open access

Abstract

Cellular membranes separate distinct aqueous compartments, but can be breached by transient hydrophilic pores. A large energetic cost prevents pore formation, which is largely dependent on the composition and structure of the lipid bilayer. The softness of bilayers and the disordered structure of pores make their characterization difficult. We use molecular-dynamics simulations with atomistic detail to study the thermodynamics, kinetics, and mechanism of pore formation and closure in DLPC, DMPC, and DPPC bilayers, with pore formation free energies of 17, 45, and 78 kJ/mol, respectively. By using atomistic computer simulations, we are able to determine not only the free energy for pore formation, but also the enthalpy and entropy, which yields what is believed to be significant new insights in the molecular driving forces behind membrane defects. The free energy cost for pore formation is due to a large unfavorable entropic contribution and a favorable change in enthalpy. Changes in hydrogen bonding patterns occur, with increased lipid-water interactions, and fewer water-water hydrogen bonds, but the total number of overall hydrogen bonds is constant. Equilibrium pore formation is directly observed in the thin DLPC lipid bilayer. Multiple long timescale simulations of pore closure are used to predict pore lifetimes. Our results are important for biological applications, including the activity of antimicrobial peptides and a better understanding of membrane protein folding, and improve our understanding of the fundamental physicochemical nature of membranes.

Cited by (0)

This is an Open Access article distributed under the terms of the Creative Commons-Attribution Noncommercial License (http://creativecommons.org/licenses/by-nc/2.0/), which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

W. F. Drew Bennett’s current address is University of Waterloo, Department of Chemistry, 200 University Avenue West, Waterloo ON, N2L 2G1.

Nicolas Sapay’s current address is BIOASTER Technology Research Institute, bâtiment Domilyon, 321 avenue Jean Jaurès, 140169007 Lyon, France.