Ion Channels in Critical Membranes: Clustering, Cooperativity, and Memory Effects

Much progress has been made in elucidating the inner workings of voltage-gated ion channels, but less understood is the influence of lipid rafts on gating kinetics. Here we propose that state-dependent channel affinity for different lipid species provides a unified explanation for the experimentally observed behaviors of clustering, cooperativity, and hysteresis. We develop models of diffusing lipids and channels engaged in Isinglike interactions to investigate the collective behaviors driven by raft formation in critical membranes close to the demixing transition. The model channels demonstrate lipid-mediated long-range interactions, activation curve steepening, and long-term memory in ionic currents. These behaviors likely play a role in channel-mediated cellular signaling and suggest a universal mechanism for self-organization of biomolecular assemblies.