Thermodynamic and Dynamic Properties of Phase-Separated Biomolecular Condensates
Biomolecular condensates, formed through phase separation, mediate crucial cellular functions and are linked with neurodegeneration and cancer. Yet we are only starting to gain a glimpse of physical understanding of their properties and complex behaviors . In this talk I will present our recent theoretical and experimental studies into the physical determinants for the thermodynamic and dynamic properties of biomolecular condensates. We found that the equilibrium of condensate formation can be regulated by adding macromolecular components, and macromolecular regulators fall into three classes, depending on whether their interactions with condensate drivers are dominated by steric repulsion, or are weakly or strongly attractive [2, 3]. The disparity in interaction strength and in structural compactness among macromolecular components leads to competition between condensate phases in space and over time , and to widely varying fusion speeds among different condensates . Probe by optical tweezers has revealed that condensates are viscoelastic rather than purely viscous . Shear relaxation spans timescales from milliseconds to seconds, and is a governing measure for dynamic processes ranging from fusion to condensate aging. These insights serve to bridge the gap in understanding between the biology and physics of biomolecular condensates.
1. H.-X. Zhou, V. Nguemaha, K. Mazarakos, and S. Qin (2018). Why do disordered and structured proteins behave differently in phase separation? Trends Biochem. Sci. 43, 499-516.
2. V. Nguemaha and H.-X. Zhou (2018). Liquid-liquid phase separation of patchy particles illuminates diverse effects of regulatory components on protein droplet formation. Sci. Rep. 8, 6728.
3. A. Ghosh, K. Mazarakos, and H.-X. Zhou (2019). Three archetypical classes of macromolecular regulators of protein liquid-liquid phase separation. Proc. Natl. Acad. Sci. USA 116, 19474-19483.
4. A. Ghosh, X. Zhang, H.-X. Zhou (2020). Tug of war between condensate phases in a minimal macromolecular system. J. Am. Chem. Soc. 142, 8848–8861.
5. A. Ghosh and H.-X. Zhou (2020). Determinants for fusion speed of biomolecular droplets. Angew. Chem. Int. Ed. 59, 20837–20840.
6. A. Ghosh, D. Kota, and H.-X. Zhou (2021). Shear relaxation governs fusion dynamics of biomolecular condensates. Nat. Commun. (accepted).
Hosted by Professor Zheng Shi