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 co...

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Published inbioRxiv
Main Authors Strom, Amy R, Kim, Yoonji, Zhao, Hongbo, Orlovsky, Natalia D, Yi-Che, Chang, Kosmirlj, Andrej, Storm, Cornelis, Brangwynne, Clifford P
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 01.03.2023
Subjects
Chromatin
Condensates
Cytoskeleton
Deoxyribonucleic acid
DNA
Gene loci
Interfaces
Phase transitions
Viscoelasticity
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Summary: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.Competing Interest StatementC.P.B. is a founder of and consultant for Nereid Therapeutics. All other authors declare no competing interests.
DOI:10.1101/2023.02.27.530281