Genome-scale single-cell mechanical phenotyping reveals disease-related genes involved in mitotic rounding

Nature Communications
Yusuke ToyodaDaniel J Müller

Abstract

To divide, most animal cells drastically change shape and round up against extracellular confinement. Mitotic cells facilitate this process by generating intracellular pressure, which the contractile actomyosin cortex directs into shape. Here, we introduce a genome-scale microcantilever- and RNAi-based approach to phenotype the contribution of > 1000 genes to the rounding of single mitotic cells against confinement. Our screen analyzes the rounding force, pressure and volume of mitotic cells and localizes selected proteins. We identify 49 genes relevant for mitotic rounding, a large portion of which have not previously been linked to mitosis or cell mechanics. Among these, depleting the endoplasmic reticulum-localized protein FAM134A impairs mitotic progression by affecting metaphase plate alignment and pressure generation by delocalizing cortical myosin II. Furthermore, silencing the DJ-1 gene uncovers a link between mitochondria-associated Parkinson's disease and mitotic pressure. We conclude that mechanical phenotyping is a powerful approach to study the mechanisms governing cell shape.

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Citations

Jul 17, 2019·Nature Nanotechnology·Morteza ArameshJános Vörös
Sep 19, 2019·Biophysics Reviews·Jochen Guck
Aug 28, 2020·Frontiers in Cell and Developmental Biology·Anna V TaubenbergerHelen K Matthews
Dec 29, 2019·Proceedings of the National Academy of Sciences of the United States of America·Benjamin M GaubDaniel J Müller
Apr 5, 2020·Nature Communications·Isma BennabiMarie-Emilie Terret
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Oct 13, 2020·Advanced Science·Kamran HosseiniElisabeth Fischer-Friedrich
Oct 22, 2020·Journal of Nanobiotechnology·Ines LüchtefeldMassimo Vassalli
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May 23, 2021·Biophysical Journal·Kamran HosseiniElisabeth Fischer-Friedrich
Jul 29, 2021·Molecular Biology of the Cell·Nilay TanejaDylan T Burnette
Oct 28, 2021·The Journal of Cell Biology·Aurélie MangonAli Badache

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Methods Mentioned

BETA
atomic force microscopy
transfection
GTPase
confocal microscopy
AFM
force measurement
X-ray

Software Mentioned

DeltaVision
Igor
AxioVision
Prism
ZEN
Igor Pro
GraphPad

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