Rheology and Viscoelasticity of Proteins and Nucleic Acids Condensates

Abstract

Phase separation is as familiar as watching vinegar separating from oil in vinegrette. The observation that phase separation of proteins and nucleic acids is widespread in living cells has opened an entire field of research into the biological significance and the biophysical mechanisms of phase separation and protein condensation in biology. Recent evidence indicate that certain proteins and nucleic acids condensates are not simple liquids and instead display both viscous and elastic behaviours, which in turn may have biological significance. The aim of this perspective is to review the state-of-the-art of this quickly emerging field focusing on the material and rheological properties of protein condensates. Finally, we discuss the different techniques that can be employed to quantify the viscoelasticity of condensates and highlight potential future directions and opportunities for interdisciplinary cross-talk between chemists, physicists and biologists.

Protein structural transitions critically transform the network connectivity and viscoelasticity of RNA-binding protein condensates but RNA can prevent it

“…Techniques such as fluorescence recovery after photobleaching (FRAP) or green florescence protein (GFP) recovery have demonstrated that over time, even condensates that start displaying liquid-like behaviour can 'age' or 'mature' (i.e., change their material properties), transitioning into gels or soft glasses [20,21,25]. Notably, particle tracking microrheology techniques have been also successfully employed to evaluate the mean squared displacement (MSD) of marked beads inside droplets, and then, via that MSD and the Stokes-Einstein relation, the viscosity of the condensates can be inferred [25,[53][54][55][56]. Moreover, the progressive dynamical arrest of proteins has been also observed in vitro for protein condensates containing marked prion-like domains (PLDs) enriched in LARKS [3,19,21,22,33,35,36,44,[57][58][59][60].…”