Biology subjects

brangwynne, C. P.

Publications and source records attributed to brangwynne, C. P..

3 recordsLinked to original sources

bioRxiv2023

Critical capillary waves of biomolecular condensates

Biomolecular condensates formed by phase separation are key players in cellular organization, yet their interfacial mechanics remain poorly understood. Here, we show that both synthetic and endogenous nuclear condensates exhibit critical-like interfacial behaviors near the phase boundary, including enhanced capillary fluctuations, critical slowing down, and reduced surface tension. By combining optogenetic control with sub-micron-resolution fluctuation spectroscopy, we quantitatively estimate surface tension, bending rigidity, and effective viscosity. Surface tension diminishes as the system approaches the critical composition, consistent with classical theories of phase separation. Notably, bending elasticity emerges as an unexpected feature of these nuclear liquid-like structures, suggesting the formation of structured interfacial layers that progressively weaken near criticality. Among these condensates, the nucleolus displayed exceptionally high viscosity, which may arise in part from viscoelastic coupling to the surrounding perinucleolar heterochromatin, effectively increasing the apparent viscosity in the long-time fluctuation regime. This non-invasive approach enables probing condensate mechanics in living cells and may provide a basis for diagnosing or modulating condensates in biomedical contexts.

biophysics↗

bioRxiv2023

Condensate-driven interfacial forces reposition DNA loci and measure chromatin viscoelasticity

Biomolecular condensates assemble in living cells through phase separation and related phase transitions. An underappreciated feature of these dynamic molecular assemblies is that they form interfaces with cellular structures, including membranes, cytoskeleton, DNA and RNA, and other membraneless compartments. These interfaces are expected to give rise to capillary forces, but there are few ways of quantifying and harnessing these forces in living cells. Here, we introduce VECTOR (ViscoElastic Chromatin Tethering and ORganization), which uses light-inducible biomolecular condensates to generate capillary forces at targeted DNA loci. VECTOR can be utilized to programmably reposition genomic loci on a timescale of seconds to minutes, quantitatively revealing local heterogeneity in the viscoelastic material properties of chromatin. These synthetic condensates are built from components that naturally form liquid-like structures in living cells, highlighting the potential role for native condensates to generate forces and do work to reorganize the genome and impact chromatin architecture.

biophysics↗

bioRxiv2022

A rich get richer effect governs intracellular condensate size distributions

Phase separation of biomolecules into condensates has emerged as a ubiquitous mechanism for intracellular organization and impacts many intracellular processes, including reaction pathways through clustering of enzymes and their intermediates. Precise and rapid spatiotemporal control of reactions by condensates requires tuning of their sizes. However, the physical processes that govern the distribution of condensate sizes remain unclear. Here, we utilize a combination of synthetic and native condensates to probe the underlying physical mechanisms determining condensate size. We find that both native nuclear speckles and FUS condensates formed with the synthetic Corelet system obey an exponential size distribution, which can be recapitulated in Monte Carlo simulations of fast nucleation followed by coalescence. By contrast, pathological aggregation of cytoplasmic Huntingtin polyQ protein exhibits a power-law size distribution, with an exponent of -1.41 {+/-} 0.02. These distinct behaviors reflect the relative importance of nucleation and coalescence kinetics: introducing continuous condensate nucleation into the Monte Carlo coarsening simulations gives rise to polyQ-like power-law behavior. We demonstrate that the emergence of power-law distributions under continuous nucleation reflects a "rich get richer" effect, whose extent may play a general role in the determination of condensate size distributions.

biophysics↗