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.

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.

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