Ion-induced transient potential fluctuations facilitate pore formation and cation transport through lipid membranes

TL;DR

This study uncovers how ion-induced potential fluctuations facilitate transient pore formation in lipid membranes, enabling unassisted ion transport, supported by microscopy and molecular dynamics simulations.

Contribution

It provides the first direct evidence linking membrane potential fluctuations to pore formation and ion transport in lipid membranes.

Findings

Membrane potential fluctuations are universal in lipid bilayers.

Potential variations lower the energy barrier for pore formation.

Transient pores enable ion flux for divalent cations.

Abstract

Unassisted ion transport through lipid membranes plays a crucial role in many cell functions without which life would not be possible, yet the precise mechanism behind the process remains unknown due to its molecular complexity. Here, we demonstrate a direct link between membrane potential fluctuations and divalent ion transport. High-throughput wide-field second harmonic (SH) microscopy shows that membrane potential fluctuations are universally found in lipid bilayer systems. Molecular dynamics simulations reveal that such variations in membrane potential reduce the free energy cost of transient pore formation and increase the ion flux across an open pore. These transient pores can act as conduits for ion transport, which we SH image for a series of divalent cations (Cu$^{2+}$, Ca$^{2+}$, Ba$^{2+}$, Mg$^{2+}$) passing through GUV membranes. Combining the experimental and computational results, we show that permeation through pores formed via an ion-induced electrostatic field is a viable mechanism for unassisted ion transport.