Abstract

Liquid-liquid phase separation has recently emerged as an important fundamental organizational phenomenon in biological settings. Most studies of biological phase separation have focused on droplets that “condense” from solution above a critical concentration, forming so-called “membraneless organelles” suspended in solution. However, membranes are ubiquitous throughout cells, and many biomolecular condensates interact with membrane surfaces. Such membrane-associated phase-separated systems range from clusters of integral or peripheral membrane proteins in the plane of the membrane to free, spherical droplets wetting membrane surfaces to droplets containing small lipid vesicles. In this review, we consider phase-separated liquids that interact with membrane surfaces and we discuss the consequences of those interactions. The physical properties of distinct liquid phases in contact with bilayers can reshape the membrane, and liquid-liquid phase separation can construct membrane-associated protein structures, modulate their function, and organize collections of lipid vesicles dynamically. We summarize the common phenomena that arise in these systems of liquid phases and membranes.

Highlights

  • Sci. 2021, 11, 1288. https://doi.org/Liquid-liquid phase separation and the formation of biomolecular condensates have recently been identified as important contributors to cellular organization

  • LAF-1, like Ddx4, undergoes phase separation driven by electrostatic interactions, and both experience an inhibitory effect from salt—increased salt concentrations increase the critical protein concentration for phase separation [6,8]

  • We have reviewed a variety of interactions between phase-separated liquids and membrane surfaces, as well as the consequences of those interactions

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Summary

Introduction

Liquid-liquid phase separation and the formation of biomolecular condensates have recently been identified as important contributors to cellular organization. The body of scientific work characterizing this collection of biomolecular condensates is ever-expanding These entities have been of scientific interest because of their seemingly widespread occurrence, and because of their versatility in function: biomolecular condensates are responsive to stimuli, concentrate biomolecules with specificity, buffer protein concentrations, and nucleate larger cellular structures, among other functions [12]. Beyond this diversity of function, liquidliquid phase separation attracts attention because it is a mechanism for the formation of so-called “membraneless organelles” [9].

Naumann
Biophysical Drivers of Liquid-Liquid Phase Separation
Stimulus Responsiveness of Biomolecular Condensates
Contact with Liquid Phases that Separate from Solution Reshapes Membranes at
Deviations from Budding: and Nanodroplets
The Formation of Some Biomolecular Condensates is Mediated by the Membrane
Biomolecular Condensates Promoting Membrane Protein Clustering Influence
Phase Separation Contributes to Nephrin Signaling
Vesicle Organization by Biomolecular Condensates Is Biologically Relevant
Active Processes and Nonequilibrium States in Cells Modify Biomolecular
Regulation of Cellular Processes Impacts Biomolecular Condensates
Conclusions
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