Condensate interfacial forces reposition DNA loci and probe chromatin viscoelasticity

Amy R Strom¹, Yoonji Kim², Hongbo Zhao³, Yi-Che Chang⁴, Natalia D Orlovsky², Andrej Košmrlj⁵, Cornelis Storm⁶, Clifford P Brangwynne⁷

Affiliations

¹ Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA.
² Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
³ Department 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.
⁴ Department of Chemistry, Princeton University, Princeton, NJ 08544, USA.
⁵ Department 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.
⁶ Eindhoven University of Technology, Department of Applied Physics and Science Education, Eindhoven, the Netherlands.
⁷ Department 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.

PMID: 39168125
DOI: 10.1016/j.cell.2024.07.034

Free article

Condensate interfacial forces reposition DNA loci and probe chromatin viscoelasticity

Amy R Strom et al. Cell. 2024.

Free article

. 2024 Sep 19;187(19):5282-5297.e20.

doi: 10.1016/j.cell.2024.07.034. Epub 2024 Aug 20.

Authors

Amy R Strom¹, Yoonji Kim², Hongbo Zhao³, Yi-Che Chang⁴, Natalia D Orlovsky², Andrej Košmrlj⁵, Cornelis Storm⁶, Clifford P Brangwynne⁷

Affiliations

¹ Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA.
² Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
³ Department 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.
⁴ Department of Chemistry, Princeton University, Princeton, NJ 08544, USA.
⁵ Department 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.
⁶ Eindhoven University of Technology, Department of Applied Physics and Science Education, Eindhoven, the Netherlands.
⁷ Department 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.

PMID: 39168125
DOI: 10.1016/j.cell.2024.07.034

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: biomolecular condensates; capillary forces; nuclear mechanics; programmable genome organization.

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Conflict of interest statement

Declaration of interests C.P.B. is a scientific founder, Scientific Advisory Board member, shareholder, and consultant for Nereid Therapeutics.

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Condensate interfacial forces reposition DNA loci and probe chromatin viscoelasticity

Affiliations

Condensate interfacial forces reposition DNA loci and probe chromatin viscoelasticity

Authors

Affiliations

Abstract

Conflict of interest statement

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Research Materials