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

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.

SUBMITTER: Layton TB

PROVIDER: S-EPMC7104857 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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

Layton Thomas B TB Williams Lynn L Colin-York Huw H McCann Fiona E FE Cabrita Marisa M Feldmann Marc M Brown Cameron C Xie Weilin W Fritzsche Marco M Furniss Dominic D Nanchahal Jagdeep J

Biology open 20200324 3

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 unco ...[more]

PMID: 32139395

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