From peptides to proteins: Uncovering the physical properties of biomolecular condensates
Liquid-liquid phase separation of biomolecules into ‘biomolecular condensates’ is emerging as a ubiquitous cellular process with misregulation of condensates increasingly implicated in disease. The emergent material properties of condensates are specifically adapted to their unique biological function and changes in property are often associated with their misregulation. It is therefore important to understand the sequence level rules governing condensate material properties and develop synthetic condensates with specific properties to act as models for these organelles. Here I will present work where, using microrheology and polymer or polymer-protein hybrid systems, we set out to determine how different residues or protein features contribute to network properties.
A number of phase separated bodies such as the nucleolus and P granules have been shown to exist as multilayered biomolecular condensates. The hierarchical organization of these multiphase droplets is dictated by material properties such as surface tension. We set out to determine whether differences between lysine and arginine condensates could be exploited to regulate multiphase dynamics and stability. We show that arginine-nucleotide droplets have approximately 100-fold greater viscosity than comparable lysine-nucleotide condensates and that the unique properties of the condensate interaction networks leads to the formation of immiscible multiphase droplets with arginine outcompeting lysine for anionic partners.
The formation of many condensates is driven by intrinsically disordered proteins or disordered regions within proteins. Consequently, much of the current understanding of biomolecular condensate property is focused on intrinsically disordered proteins and has been informed by simplified models of complex coacervation of oppositely charged polyelectrolytes. However, as the majority of proteins have a folded globular structure, it is crucial to understand the impact of folded domains on condensate properties. I will also present my most recent work in which we set out to determine how protein charge distribution across folded domains and biomacromolecule ratio contribute towards network properties.
Hosted by Professor Wilma Olson
~Coffee/tea will be served prior to the lecture~