Phase separation and critical size in molecular sorting

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 [M. Zamparo, D. Valdembri, G. Serini, I. V. Kolokolov, V. V. Lebedev, L. Dall'Asta, and A. Gamba, Phys. Rev. Lett. 126, 088101 (2021)], 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 and unproductive domains inferred from experimental data are in agreement with those predicted from numerical simulations of the model, compatibly with the hypothesis that molecular sorting is driven by a phase separation process.

Automated summary

Molecular sorting is a crucial process in eukaryotic cells that allows for the concentration of specific chemical factors in different cell membrane subregions, giving them distinct chemical identities and functional properties. A recent phenomenological theory proposes that molecular sorting arises from phase separation-driven sorting domains and domain-induced membrane bending, resulting in the formation of lipid vesicles enriched in the sorted molecules. The efficiency of molecular distillation is found to be influenced by the critical size of phase separated domains. Experimental observations show that sorting domains can be classified into unproductive and productive domains, with the latter evolving into vesicles that detach from the membrane system. The study discusses the implications of this classification within the framework of the phenomenological theory and verifies several predictions through numerical simulations. The analysis reveals that sorting is most efficient when the number of sorting domains is close to a minimum, and introduces an operational definition of the critical size of sorting domains to aid in the analysis of experimental data. Comparison with experimental results suggests that the statistical properties of productive and unproductive domains inferred from experimental data align with those predicted by numerical simulations, supporting the hypothesis that molecular sorting is driven by a phase separation process.