Abstract
Biomolecular condensates, formed through liquid-liquid 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 [1]. In this talk I will present our recent theoretical and experimental studies into the physical determinants for the thermodynamic and material 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 architypes, depending on whether their interactions with condensate drivers are dominated by steric repulsion, or are weakly or strongly attractive [2, 3]. Matching effects of macromolecular regulators on phase equilibrium and on interfacial tension are predicted from computational studies [4] and confirmed experimentally [5]. The disparity in interaction strength and in structural compactness among macromolecular components leads to multiphase organization [6,7], and to widely varying fusion speeds among different condensates [8]. Probe by optical tweezers has revealed that condensates are viscoelastic rather than purely viscous [9]. Shear thinning allows condensates to remain extremely dynamic, as required for cellular functions, despite the high macroscopic viscosity [10]. These insights serve to bridge the gap in understanding between the biology and physics of biomolecular condensates.
References
1. H.-X. Zhou, V. Nguemaha, K. Mazarakos, and S. Qin (2018). Trends Biochem. Sci. 43, 499-516.
2. V. Nguemaha and H.-X. Zhou (2018). Sci. Rep. 8, 6728.
3. A. Ghosh, K. Mazarakos, and H.-X. Zhou (2019). Proc. Natl. Acad. Sci. USA 116, 19474-19483.
4. K. Mazarakos and H.-X. Zhou (2021). Protein Sci. 30, 1360-1370.
5. D. Kota and H.-X. Zhou (2022). J. Phys. Chem. Lett. 13, 5285-5290.
6. K. Mazarakos and H.-X. Zhou (2022). J. Chem. Phys. 156, 191104.
7. A. Ghosh, X. Zhang, H.-X. Zhou (2020). J. Am. Chem. Soc. 142, 8848–8861.
8. A. Ghosh and H.-X. Zhou (2020). Angew. Chem. Int. Ed. 59, 20837–20840.
9. A. Ghosh, D. Kota, and H.-X. Zhou (2021). Nat. Commun. 12, 5995.
10. D. Kota, R. Prasad, and H.-X. Zhou (2023). bioRxiv.
Please contact phweb@ust.hk should you have questions about the talk.
