Open Conference Systems, StatPhys 27 Main Conference

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Physical determinants of liquid-liquid phase separation of proteins mixtures
Jorge R. Espinosa

##manager.scheduler.building##: Edificio San Alberto Magno
##manager.scheduler.room##: Auditorio Santa Cecilia
Date: 2019-07-12 12:30 PM – 12:45 PM
Last modified: 2019-06-09

Abstract


The cell interior contains heterogenous mixtures of thousands of different components that need to be organized in space to facilitate control of function. Such organization is achieved through the formation of organelles that are enclosed by physical membranes and membraneless cellular bodies that are sustained by the physical chemistry of Liquid-Liquid Phase Separation (LLPS)[1,2]. Cellular bodies are liquid-like domains that emerge spontaneoulsy above a critical concentration in mixtures of interacting multivalent proteins and nucleic-acids. Here we uncover the physical determinants that explain control of composition and stability of phase-separated cellular bodies formed by mixtures of proteins with different valencies, topologies, and interaction energies. By combining the well-established physics of self-assembly of colloidal patchy particles with a novel continuous potential optimized for fast and scalable molecular dynamics simulations, we show that when proteins mixtures undergo LLPS, the resulting coexisting phases exhibit  inhomogeneous compositions. We demonstrate that the probability of a given protein to concentrate in the condensed versus the diluted liquid phase in a multi-component mixture correlates with the critical temperature for LLPS of the pure single-component protein system.
We determine that the critical temperature of a single-component protein solution and, in consequence,
the expected concentration of such protein in a condensed multi-component cellular body, increase with the valency of the protein, promiscuous rather than selective binding, stronger protein-protein interaction energies, and distributions of binding sites that do not disfavour formation of a percolating network. Our results show a general mechanisms by which cells can easily control the stability and composition of their liquid-liquid coexisting phases: proteins that concentrate in the condensed phase can decrease more significantly their enthalpic contribution to the free energy of the system via their strong protein-protein interactions, while proteins that concentrate in the diluted phase cannot compete with their higher valency partners and instead are segregated to the diluted phase where their proteinprotein interactions are minimized and their entropy maximised.

References:

1) Larson et al, Nature, 547, 236 (2017)

2) Strom et al, Nature, 547, 241 (2017)