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

Layton TB., Williams L., Colin-York H., McCann FE., Cabrita M., Feldmann M., Brown C., Xie W., Fritzsche M., Furniss D., Nanchahal J.

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.

DOI

10.1242/bio.049809

Type

Journal article

Journal

Biol open

Publication Date

24/03/2020

Volume

9

Keywords

Focal adhesion, Myofibroblast, Single cell, Traction force, Biomarkers, Biomechanical Phenomena, Biophysical Phenomena, Cells, Cultured, Cytoskeleton, Fluorescent Antibody Technique, Humans, Molecular Imaging, Myofibroblasts, Single-Cell Analysis

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