A minimal model of plasma membrane heterogeneity requires coupling cortical actin to criticality

TL;DR

This paper introduces a minimal model combining criticality and cortical actin connectivity to explain plasma membrane heterogeneity, reproducing experimental observations of fluctuations and component segregation.

Contribution

It develops a simple coupled Ising and cytoskeleton model that captures critical fluctuations and membrane heterogeneity observed experimentally.

Findings

Critical fluctuations cause small, dynamic membrane fluctuations.

Cytoskeleton coupling prevents large phase separation at physiological temperatures.

Criticality enables long-range organization and segregation of membrane components.

Abstract

We present a minimal model of plasma membrane heterogeneity that combines criticality with connectivity to cortical cytoskeleton. Our model is motivated by recent observations of micron-sized critical fluctuations in plasma membrane vesicles that are detached from their cortical cytoskeleton. We incorporate criticality using a conserved order parameter Ising model coupled to a simple actin cytoskeleton interacting through point-like pinning sites. Using this minimal model, we recapitulate several experimental observations of plasma membrane raft heterogeneity. Small (r~20nm) and dynamic fluctuations at physiological temperatures arise from criticality. Including connectivity to cortical cytoskeleton disrupts large fluctuations, prevents macroscopic phase separation at low temperatures (T<=22{\deg}C), and provides a template for long lived fluctuations at physiological temperature (T=37{\deg}C). Cytoskeleton-stabilized fluctuations produce significant barriers to the diffusion of some membrane components in a manner that is weakly dependent on the number of pinning sites and strongly dependent on criticality. More generally, we demonstrate that critical fluctuations provide a physical mechanism to organize and spatially segregate membrane components by providing channels for interaction over large distances.