  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 Ising-like 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.
