Minimal Model of Plasma Membrane Heterogeneity Requires Coupling Cortical Actin to Criticality

Abstract

We present a minimal model of plasma membrane heterogeneity that combines criticality with connectivity to cortical cytoskeleton. The development of this model was 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 ∼ 20 nm) and dynamic fluctuations at physiological temperatures arise from criticality. Including connectivity to the cortical cytoskeleton disrupts large fluctuations, prevents macroscopic phase separation at low temperatures (T ≤ 22°C), and provides a template for long-lived fluctuations at physiological temperature (T = 37°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 for organizing and spatially segregating membrane components by providing channels for interaction over large distances.

Transient subdiffusion from an Ising environment

“…As commented in Sec. I, such distribution has been used to describe the heterogeneities present in plasma membranes [13,14]. In this context, relating P (κ) to such distribution of sizes provides a way to connect spatio-temporal properties of the environment at criticality to the stemming of subdiffusion, and thus offers an analytical tool to study their interplay.…”

“…Besides membrane proteins, the lipids -the most abundant components of the * miguel.garcia-march@icfo.es cell membrane -contribute to this heterogeneous organization by interacting with cholesterol, proteins and the cytoskeleton in order to partition the membrane [11], as a consequence of these dynamic interactions, also lipids exhibit non-Brownian diffusion behavior [12]. Due to the presence of miscibility critical points and associated long-range critical fluctuations, the compositional heterogeneity of the plasma membranes has been often modeled as a nearly critical environment through an Ising model [13,14].…”

Membrane heterogeneity: Manifestation of a curvature-induced microemulsion

“…Again the size of these fluctuations are proposed to be limited by the cytoskelton 13 . This hypothesis is not only subject to the criticism that there may be no miscibility phase transition nearby, but also to the observation that fluctuations near a critical point exhibit little difference between their composition and that of the background from which they arise.…”

Equilibrium microphase separation in the two-leaflet model of lipid membranes

“…In nonequilibrium systems, an analog of the microphase separation can be observed when energetically activated reactions between two components are included [5,6]. The nonequilibrium scenario has inspired a variety of proposals in the context of the cell membrane [7][8][9][10][11][12].Equilibrium microphase separation in two-component lipid membranes was found in two-leaflet models with different lipid composition in each leaflet [13][14][15][16]. In these models, coupling between the local membrane curvature and the difference of local lipid compositions in two layers could give rise to an instability at finite wave numbers.…”

“…In nonequilibrium systems, an analog of the microphase separation can be observed when energetically activated reactions between two components are included [5,6]. The nonequilibrium scenario has inspired a variety of proposals in the context of the cell membrane [7][8][9][10][11][12].…”