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Condensate interfacial forces reposition DNA loci and probe chromatin viscoelasticity

Affiliations
  • 1Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA.
  • 2Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
  • 3Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA; Department of Mechanical and Aerospace Engineering, Princeton, NJ 08544, USA; Omenn-Darling Bioengineering Institute, Princeton University, Princeton, NJ 08544, USA.
  • 4Department of Chemistry, Princeton University, Princeton, NJ 08544, USA.
  • 5Department of Mechanical and Aerospace Engineering, Princeton, NJ 08544, USA; Omenn-Darling Bioengineering Institute, Princeton University, Princeton, NJ 08544, USA; Princeton Materials Institute, Princeton University, Princeton, NJ 08544, USA.
  • 6Eindhoven University of Technology, Department of Applied Physics and Science Education, Eindhoven, the Netherlands.
  • 7Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA; Omenn-Darling Bioengineering Institute, Princeton University, Princeton, NJ 08544, USA; Princeton Materials Institute, Princeton University, Princeton, NJ 08544, USA; Howard Hughes Medical Institute, Chevy Chase, MD 21044, USA. Electronic address: cbrangwy@princeton.edu.

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August 21, 2024

Abstract

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 other 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 viscoelastic chromatin tethering and organization (VECTOR), 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.

Keywords:

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