Self-Organization of a Stable Pore Structure in a Phospholipid Bilayer

We demonstrate the self-organization process of a stable pore structure in a phospholipid bilayer by unsteady and nonequilibrium molecular dynamics simulations. The simulation is started from an initial state including some amount of water molecules in its hydrophobic region, which is a model of a cell membrane stimulated by ultrasound radiation for the membrane permeabilization (sonoporation). We show that, in several nanoseconds, the bilayer-water system can spontaneously develop into a water-filled pore structure without any mechanical and electrical forcing from outside, when the initial number of water molecules in the hydrophobic region exceeds a critical value. The increase in the initial number of water molecules enhances the probability of pore formation, and sometimes induces the formation of transient micellelike structures of phospholipid molecules.

Figure 1

Snapshots of a typical process of the spontaneous pore formation: (a) $t=0\mathrm{ps}$, (b) $t=600\mathrm{ps}$, and (c) $t=2000\mathrm{ps}$. Panel (d) is the top view of the pore and only chains are shown and Panels (e) and (f) are the side views of micellelike and multipore structures, respectively. The headgroups of lipids are shown in yellow bars, the hydrophobic chains in orange bars, water molecules initially outside the bilayer are shown in red spheres, and the water molecules inserted are shown in blue spheres. The white bar in Panels (a), (e), and (f) corresponds to 4 nm.

Figure 2

Temporal changes of $R(t)$ for the initial 10 ns. The symbols are plotted at every 0.5 ns and curves are smoothed by a running average.

Figure 3

Schematic picture of the self-organization process of bilayer initially including water molecules in its hydrophobic region.