Sorting of multiple molecular species on cell membranes

TL;DR

This study extends a physical model of molecular sorting on cell membranes to multiple species, revealing how heterogeneity, affinity, and valence influence sorting efficiency and capacity in biological membranes.

Contribution

The paper introduces a model for simultaneous sorting of multiple molecular species on membranes, analyzing effects of heterogeneity, affinity, and valence on sorting efficiency.

Findings

Sorting time increases with molecular heterogeneity according to a scaling law.

Multiple species can be sorted in parallel without significant interference.

Sorting efficiency is higher when species have similar homotypic affinities.

Abstract

Eukaryotic cells maintain their inner order by a hectic process of distillation of molecular factors taking place on the surface of their lipid membranes. To understand the properties of this molecular sorting process, a physical model of the process has been recently proposed [arXiv:1811.06760], based on (a) the phase separation of a single, initially dispersed molecular species into spatially localized sorting domains on the lipid membrane, and (b) 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 has shown the existence of an optimal region of the 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 a typical cell membrane region 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.