Biological soft matter: intrinsically disordered proteins in liquid-liquid phase separation and biomolecular condensates

Abstract

The facts that many proteins with crucial biological functions do not have unique structures and that many biological processes are compartmentalized into the liquid-like biomolecular condensates, which are formed via liquid-liquid phase separation (LLPS) and are not surrounded by the membrane, are revolutionizing the modern biology. These phenomena are interlinked, as the presence of intrinsic disorder represents an important requirement for a protein to undergo LLPS that drives biogenesis of numerous membrane-less organelles (MLOs). Therefore, one can consider these phenomena as crucial constituents of a new IDP-LLPS-MLO field. Furthermore, intrinsically disordered proteins (IDPs), LLPS, and MLOs represent a clear link between molecular and cellular biology and soft matter and condensed soft matter physics. Both IDP and LLPS/MLO fields are undergoing explosive development and generate the ever-increasing mountain of crucial data. These new data provide answers to so many long-standing questions that it is difficult to imagine that in the very recent past, protein scientists and cellular biologists operated without taking these revolutionary concepts into account. The goal of this essay is not to deliver a comprehensive review of the IDP-LLPS-MLO field but to provide a brief and rather subjective outline of some of the recent developments in these exciting fields.

Keywords: Intrinsically disordered protein; Liquid-liquid phase separation; Membraneless organelle; Protein-protein interactions; Soft matter; Water structure.