Phase separation and critical size in molecular sorting

TL;DR

This paper presents a phenomenological theory of molecular sorting based on phase separation and membrane bending, emphasizing the role of critical domain size in sorting efficiency, supported by numerical simulations and experimental data comparison.

Contribution

It introduces a new operational definition of critical domain size and links phase separation theory to molecular sorting efficiency, validated through simulations and experiments.

Findings

Sorting efficiency peaks near a minimal number of domains

Productive and unproductive domains correspond to subcritical and supercritical phases

Experimental data aligns with model predictions on domain properties

Abstract

Molecular sorting is a fundamental process that allows eukaryotic cells to distill and concentrate specific chemical factors in appropriate cell membrane subregions, thus endowing them with different chemical identities and functional properties. A phenomenological theory of this molecular distillation process has recently been proposed [arXiv:1811.06760], based on the idea that molecular sorting emerges from the combination of: a) phase-separation-driven formation of sorting domains, and b) domain-induced membrane bending, leading to the production of submicrometric lipid vesicles enriched in the sorted molecules. In this framework, a natural parameter controlling the efficiency of molecular distillation is the critical size of phase-separated domains. In the experiments, sorting domains appear to fall into two classes: unproductive domains, characterized by short lifetimes and low probability of extraction, and productive domains, that evolve into vesicles that ultimately detach from the membrane system. It is tempting to link these two classes to the different fates predicted by classical phase separation theory for subcritical and supercritical phase-separated domains. Here, we discuss the implication of this picture in the framework of the previously introduced phenomenological theory of molecular sorting. Several predictions of the theory are verified by numerical simulations of a lattice-gas model. Sorting is observed to be most efficient when the number of sorting domains is close to a minimum. To help in the analysis of experimental data, an operational definition of the critical size of sorting domains is proposed. Comparison with experimental results shows that the statistical properties of productive/unproductive domains inferred from experimental data are in agreement with those predicted from numerical simulations of the model.