Molecular dynamics simulation of cell membrane pore sealing

Biological membranes play a pivotal role in almost all cellular phenomena as highly versatile physiological and functional platforms for signalling and interacting lipids and proteins. Membrane integrity can be disrupted by diseases, mechanical trauma, and therapeutic processes, potentially causing deleterious effects including cell death. Membrane perforation, purposely-induced or undesired, is a basic perturbation to the membrane's structural integrity, and can significantly influence a cell membrane's biomechanical and biophysical properties. However, the molecular mechanisms by which membrane pores dynamically respond to various loading conditions are still not well understood. By combining biomolecular simulations with multiscaling tools, this study quantitatively examines the dynamics of membrane pore sealing process at atomistic resolution in consistence with continuum mechanics concepts. Here, we consider hydrated lipid bilayer membranes with circular pores of various diameters (similar to 5 - 120 angstrom) under constant pressure (1 atm) and temperature (310 K). Over the course of rapidly evolving sealing events, the continuum-like deformation characteristics of membranes are characterised based on molecular dynamics simulation results. We find that the membrane's areal strain histories exhibit appreciable sensitivity to the pore sizes, and that the membrane's out-of-plane strain evolution reflects its key structural alterations observed in the simulations. Water permeation is explored by quantifying the number of water molecules transferred from their initial layers through the pore to the opposite sides. Under the applied sealing conditions, our results suggest that both the water transport and time duration of membrane sealing markedly depend on the pore sizes. This work provides a computational framework aimed at probing transient biomolecular/cellular processes and providing insights into the mechanistic underpinnings of post-poration molecular transport to further manipulate/control them for biomedical applications. (C) 2019 Elsevier Ltd. All rights reserved.