An alternative scenario for the formation of specialized protein nano-domains (cluster phases) in biomembranes

TL;DR

This paper proposes a new explanation for the formation of specialized protein nano-domains in cell membranes, emphasizing protein interactions and entropy without relying on lipid micro-phase separation.

Contribution

It introduces a realistic scenario for membrane domain formation based on protein affinities and entropy, challenging the lipid raft hypothesis.

Findings

Protein sorting can occur without lipid micro-phase separation.

The scenario aligns with known physical interactions among membrane proteins.

Membrane domains can form with thousands of protein species coexisting.

Abstract

We discuss a realistic scenario, accounting for the existence of sub-micrometric protein domains in cell membranes. At the biological level, such membrane domains have been shown to be specialized, in order to perform a determined biological task, in the sense that they gather one or a few protein species out of the hundreds of different ones that a cell membrane may contain. By analyzing the balance between mixing entropy and protein affinities, we propose that such protein sorting in distinct domains can be explained without appealing to pre-existing lipidic micro-phase separations, as in the lipid raft scenario. We show that the proposed scenario is compatible with known physical interactions between membrane proteins, even if thousands of different species coexist.