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March 31st, 2025
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Harvard University
biophysics
biorxiv

The Origin of the Ionic-strength Dependent Reentrant Behavior in Liquid-Liquid Phase Separation of Neutral IDPs

Mondal, S.Open in Google Scholar•Shakhnovich, E.Open in Google Scholar

The effect of salt on coacervation of synthetic or biological polyelectrolytes is well-studied. However, recent experiments showed that largely neutral IDPs like FUS also undergo LLPS at physiological salt concentrations, dissolve at higher salt concentration and again phase separate at higher salt concentrations such as, [Cion][~]3M. Here we use analytical theory and simulations to reveal the mechanism of these transitions. At low [Cion], the ionic solution acts as a highly correlated medium conferring long-range effective attractive interactions between spatially distant FUS monomers. In this regime the ion concentration inside the condensate is higher than in the bulk solution. As [Cion] increases, the correlation length in the ionic plasma decreases, and the condensate dissolves. Second LLPS at high [Cion] is due to the entropy-driven crowding, and ion concentration inside the condensate is lower than in the bulk. Our study unravels a general physical mechanism of salt-dependent reentrant behavior in LLPS in neutral IDPs.

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