Fast and synchronized fluctuations of cortical actin negatively correlate with nucleoli liquid–liquid phase separation in T cells

Ishay Wohl, Oren Yakovian, Yair Razvag, Meital Reches, Eilon Sherman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Liquid–liquid phase separation is an important mechanism by which eukaryotic cells functionally organize their intracellular content and has been related to cell malignancy and neurodegenerative diseases. These cells also undergo ATP-driven mechanical fluctuations, yet the effect of these fluctuations on the liquid–liquid phase separation remains poorly understood. Here, we employ high-resolution microscopy and atomic force microscopy of live Jurkat T cells to characterize the spectrum of their mechanical fluctuations, and to relate these fluctuations to the extent of nucleoli liquid–liquid phase separation (LLPS). We find distinct fluctuation of the cytoskeleton and of the cell diameter around 110 Hz, which depend on ATP and on myosin activity. Importantly, these fluctuations negatively correlate to nucleoli LLPS. According to a model of cell viscoelasticity, we propose that these fluctuations generate mechanical work that increases intracellular homogeneity by inhibiting LLPS. Thus, active mechanical fluctuations serve as an intracellular regulatory mechanism that could affect multiple pathophysiological conditions.

Original languageAmerican English
Pages (from-to)409-423
Number of pages15
JournalEuropean Biophysics Journal
Volume49
Issue number6
DOIs
StatePublished - 1 Sep 2020

Bibliographical note

Publisher Copyright:
© 2020, European Biophysical Societies' Association.

Keywords

  • Cortical actin
  • DFT analysis
  • Fluctuation
  • Liqud–liquid phase separation
  • Myosin
  • Nucleoli
  • Plasma membrane
  • Tension

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