Single cell force profiling of human myofibroblasts reveals a biophysical spectrum of cell states.

Biology Open
Thomas B LaytonJagdeep Nanchahal

Abstract

Mechanical force is a fundamental regulator of cell phenotype. Myofibroblasts are central mediators of fibrosis, a major unmet clinical need characterised by the deposition of excessive matrix proteins. Traction forces of myofibroblasts play a key role in remodelling the matrix and modulate the activities of embedded stromal cells. Here, we employ a combination of unsupervised computational analysis, cytoskeletal profiling and single cell traction force microscopy as a functional readout to uncover how the complex spatiotemporal dynamics and mechanics of living human myofibroblast shape sub-cellular profiling of traction forces in fibrosis. We resolve distinct biophysical communities of myofibroblasts, and our results provide a new paradigm for studying functional heterogeneity in human stromal cells.

References

May 1, 1983·The Journal of Hand Surgery·M A BadalamenteL C Hurst
Nov 1, 1996·The Journal of Hand Surgery·G M RayanJ J Tomasek
Sep 13, 2001·Molecular Biology of the Cell·B HinzC Chaponnier
Jul 5, 2003·American Journal of Physiology. Heart and Circulatory Physiology·J WangC A McCulloch
Oct 29, 2003·Current Opinion in Biotechnology·Boris Hinz, Giulio Gabbiani
Jan 13, 2006·The Journal of Cell Biology·Jérôme M GoffinBoris Hinz
Nov 17, 2009·The Journal of Hand Surgery·Liaquat Suleman VerjeeJagdeep Nanchahal
Sep 8, 2011·Journal of Visualized Experiments : JoVE·Fei Liu, Daniel J Tschumperlin
Jun 5, 2012·American Journal of Physiology. Lung Cellular and Molecular Physiology·Aleksandar MarinkovićDaniel J Tschumperlin
Jul 10, 2012·Nature Medicine·Thomas A Wynn, Thirumalai R Ramalingam
Feb 23, 2013·Proceedings of the National Academy of Sciences of the United States of America·Liaquat S VerjeeJagdeep Nanchahal
Dec 17, 2014·American Journal of Physiology. Lung Cellular and Molecular Physiology·Fei LiuDaniel J Tschumperlin
Mar 1, 2016·Nano Letters·Huw Colin-YorkMarco Fritzsche
Apr 29, 2016·Nature Methods·William J Polacheck, Christopher S Chen
Jul 2, 2016·Fibrogenesis & Tissue Repair·Marike M van BeugeRuud A Bank
Mar 17, 2017·Nature Protocols·Huw Colin-YorkMarco Fritzsche
Mar 21, 2019·Cell Reports·Huw Colin-YorkMarco Fritzsche
Jun 15, 2019·Nano Letters·Huw Colin-YorkMarco Fritzsche

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Citations

Aug 9, 2020·Experimental Dermatology·Abigail De La PenaChelsey S Simmons
Aug 8, 2020·Proceedings of the National Academy of Sciences of the United States of America·Lynn M WilliamsJagdeep Nanchahal
Jan 16, 2021·Biomechanics and Modeling in Mechanobiology·Claudie PetitStéphane Avril

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Methods Mentioned

BETA
force measurements
atomic force microscopy
AFM
PCA
RNA-seq

Software Mentioned

3D
R
OrientationJ
Bioformats
igraph R
stats
ggplot2
MATLAB
R package ‘ cccd ’
R R

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