Seminar - Nicola Galvanetto

Biomolecular condensates are droplets-like structures originating from the phase-separation of biomolecules. The functions of condensates within living cells span many length scales: from the modulation of chemical reactions at the molecular scale to the compartmentalization of the cell at the mesoscale. We employ single-molecule fluorescence spectroscopy to study the conformations and dynamics of intrinsically disordered proteins within single droplets (1), combined with microrheology approaches to assess mesoscale properties. By tuning the strength of the interactions among the constituent proteins, we produced condensates spanning almost two orders of magnitude in viscosity. We find that the nanoscale chain dynamics on the nano- to microsecond timescale can be accurately related to both translational diffusion and mesoscale condensate viscosity by analytical relations from polymer physics (2). Atomistic simulations reveal that the differences in friction — a key quantity underlying these relations — are caused by differences in inter-residue contact lifetimes, thereby leading to the vastly different dynamics among the condensates.
I will also discuss how these methods can be used to study i) protein aging, which occurs at the surface of droplets and induces protein aggregation which is toxic for the cells (3), and ii) how electric fields can alter the affinity and diffusivity of biomolecules, inducing or disrupting aggregation (4).

N. Galvanetto, Dpt of Biochemistry & Dpt of Physics, Univ. of Zurich, Switzerland

1.            N. Galvanetto, et al., Extreme dynamics in a biomolecular condensate. Nature 619, 876–883 (2023).

2.            N. Galvanetto, et al., Mesoscale properties of biomolecular condensates emerging from protein chain dynamics. arXiv:2407.19202  (2024).

3.            M. Linsenmeier, et al., The interface of condensates of the hnRNPA1 low-complexity domain promotes formation of amyloid fibrils. Nat. Chem. 15, 1340–1349 (2023).

4.            M. Lechelon, et al., Experimental evidence for long-distance electrodynamic intermolecular forces. Science Advances 8, eabl5855 (2022).