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Lee, D. S. W.

Publications and source records attributed to Lee, D. S. W..

2 recordsLinked to original sources

Mechanical frustration of phase separation in the cell nucleus by chromatin

Liquid-liquid phase separation is a fundamental mechanism underlying subcellular organization. Motivated by the striking observation that optogenetically-generated droplets in the nucleus display suppressed coarsening dynamics, we study the impact of chromatin mechanics on droplet phase separation. We combine theory and simulation to show that crosslinked chromatin can mechanically suppress droplets coalescence and ripening, as well as quantitatively control their number, size, and placement. Our results highlight the role of the subcellular mechanical environment on condensate regulation.

biophysics

Chromatin Mechanics Dictates Subdiffusion and Coarsening Dynamics of Embedded Condensates

DNA is organized into chromatin, a complex polymeric material which stores information and controls gene expression. An emerging mechanism for biological organization, particularly within the crowded nucleus, is biomolecular phase separation into condensed droplets of protein and nucleic acids. However, the way in which chromatin impacts the dynamics of phase separation and condensate formation is poorly understood. Here, we utilize a powerful optogenetic strategy to examine the interplay of droplet coarsening with the surrounding viscoelastic chromatin network. We demonstrate that droplet growth dynamics are directly inhibited by the chromatin-dense environment, which gives rise to an anomalously slow coarsening exponent, {beta}[~]0.12, contrasting with the classical prediction of {beta}[~] 1/3. Using scaling arguments and simulations, we show how this arrested growth can arise due to subdiffusion of individual condensates, predicting {beta}[~]/3, where is the diffusion exponent. Tracking the fluctuating motion of condensates within chromatin reveals a subdiffusive exponent, [~]0.5, which explains the anomalous coarsening behavior and is also consistent with Rouse-like dynamics arising from the entangled chromatin. Our findings have implications for the biophysical regulation of the size and shape of biomolecular condensates, and suggest that condensate emulsions can be used to probe the viscoelastic mechanical environment within living cells.

biophysics