Allosteric Regulation by a Critical Membrane

TL;DR

This paper investigates how the proximity of cell membranes to a critical point influences ion channel regulation and activity, revealing enhanced sensitivity and complex dynamics due to critical phenomena.

Contribution

It introduces a theoretical framework linking membrane criticality to allosteric regulation of proteins, using Ising models to explore emergent behaviors.

Findings

Protein activity is highly sensitive to membrane perturbations near criticality.

Membrane criticality induces a broad spectrum of protein kinetic time scales.

Critical fluctuations lead to non-Markovian protein dynamics.

Abstract

Many of the processes that underly neural computation are carried out by ion channels embedded in the plasma membrane, a two-dimensional liquid that surrounds all cells. Recent experiments have demonstrated that this membrane is poised close to a liquid-liquid critical point in the Ising universality class. Here we use both exact and stochastic techniques on the lattice Ising model to explore the ramifications of proximity to criticality for proteins that are allosterically coupled to Ising composition modes. Owing to diverging generalized susceptibilities, such a protein's activity becomes strongly influenced by perturbations that influence the two relevant parameters of the critical point, especially the critical temperature. In addition, the protein's kinetics acquire a range of time scales from its surrounding membrane, naturally leading to non-Markovian dynamics.