Sorting of multiple molecular species on cell membranes.

Abstract

Eukaryotic cells maintain their inner order by a hectic process of sorting and distillation of molecular factors taking place on their lipid membranes. A similar sorting process is implied in the assembly and budding of enveloped viruses. To understand the properties of this molecular sorting process, we have recently proposed a physical model [Zamparo et al., Phys. Rev. Lett. 126, 088101 (2021)]10.1103/PhysRevLett.126.088101, based on (1) the phase separation of a single, initially dispersed molecular species into spatially localized sorting domains on the lipid membrane and (2) domain-induced membrane bending leading to the nucleation of submicrometric lipid vesicles, naturally enriched in the molecules of the engulfed sorting domain. The analysis of the model showed the existence of an optimal region of parameter space where sorting is most efficient. Here the model is extended to account for the simultaneous distillation of a pool of distinct molecular species. We find that the mean time spent by sorted molecules on the membrane increases with the heterogeneity of the pool (i.e., the number of distinct molecular species sorted) according to a simple scaling law, and that a large number of distinct molecular species can in principle be sorted in parallel on cell membranes without significantly interfering with each other. Moreover, sorting is found to be most efficient when the distinct molecular species have comparable homotypic affinities. We also consider how valence (i.e., the average number of interacting neighbors of a molecule in a sorting domain) affects the sorting process, finding that higher-valence molecules can be sorted with greater efficiency than lower-valence molecules.