FlickerPRINT for Harnessing Shape Fluctuations to Probe the Mechanics of Biomolecular Condensates

Abstract

Many biomolecular condensates are liquid-like droplets composed of proteins and/or RNAs, and a key mechanical property for any liquid droplet is its surface tension. Here, I will discuss the need to measure its value in living cells and present our recently developed high-throughput flicker spectroscopy approach to calculate the surface tension of biomolecular condensates.

Demonstrating this approach on stress granules, we show that a surface tension-only model is inadequate for describing stress granules in live cells. We find that the measured fluctuation spectra require an additional bending rigidity parameter, which supports the view that stress granules are viscoelastic droplets with a structured interface. Pleasingly, the approach can distinguish stress granules induced by different chemicals or under different stoichiometries of constituent proteins, or in senescent cells, based on their characteristic distributions of surface tension and bending rigidity values.

Taken together, these results demonstrate quantitatively that the mechanics of stress granules clearly deviate from those expected for simple liquid droplets and instead suggest that stress granules are viscoelastic droplets with a structured interface. We also note that the measured surface tensions and bending rigidities span a range of several orders of magnitude. As such, different types of stress granules (and more generally, other biomolecular condensates) can only be differentiated via large-scale surveys.

Sushma Nagaraja Grellscheid

Professor, Computational Biology Unit, University of Bergen, Norway,
Professor of Genomics, Durham University, UK
Correspondence: sushma@cantab.net

Short Bio

Sushma Grellscheid is a Professor of Genomics at the Computational Biology Unit at the University of Bergen, Norway and heads ELIXIR Norway, the Norwegian part of the pan-European infrastructure for life sciences data. She is also a professor of genomics at Durham University, UK.

She received her PhD in RNA Biochemistry in 2004 from the University of Cambridge, UK. Her post-doctoral work at the University of Cologne and Newcastle University was on RNA alternative splicing regulation in Human Genetics, and Ageing followed by research fellowships at the European Bioinformatics Institute (EMBL-EBI, Cambridge, 2011-2012), and Durham University (Addison Wheeler 2012-2015). She was appointed Assistant Professor in RNA Genomics at Durham University in October 2015 (continuing part-time), and Professor at CBU and Bio at the University of Bergen in 2018.

Her research group members are interested in combining molecular biology, computational biology and biophysics approaches to understanding RNA mediated cellular physiology, especially relating to cellular physics of biomolecular condensates. They are actively working on projects involving alternative splicing regulation, condensate biology, ageing and senescence.