A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Directed cell migration towards softer environments
Tekijät: Isomursu Aleksi, Park Keun-Young, Hou Jay, Cheng Bo, Mathieu Mathilde, Shamsan Ghaidan A., Fuller Benjamin, Kasim Jesse, Mahmoodi M. Mohsen, Lu Tian Jian, Genin Guy M., Xu Feng, Lin Min, Distefano Mark D., Ivaska Johanna, Odde David J.
Kustantaja: Nature Portfolio
Julkaisuvuosi: 2022
Journal: Nature Materials
Tietokannassa oleva lehden nimi: NATURE MATERIALS
Lehden akronyymi: NAT MATER
Vuosikerta: 21
Aloitussivu: 1081
Lopetussivu: 1090
Sivujen määrä: 17
ISSN: 1476-1122
eISSN: 1476-4660
DOI: https://doi.org/10.1038/s41563-022-01294-2
Verkko-osoite: https://www.nature.com/articles/s41563-022-01294-2
Tiivistelmä
Directed cell movement known as durotaxis, typically associated with cellular migration in response to a substrate gradient of increasing stiffness, is now shown to also occur in the opposite direction, following a gradient of decreasing stiffness.How cells sense tissue stiffness to guide cell migration is a fundamental question in development, fibrosis and cancer. Although durotaxis-cell migration towards increasing substrate stiffness-is well established, it remains unknown whether individual cells can migrate towards softer environments. Here, using microfabricated stiffness gradients, we describe the directed migration of U-251MG glioma cells towards less stiff regions. This 'negative durotaxis' does not coincide with changes in canonical mechanosensitive signalling or actomyosin contractility. Instead, as predicted by the motor-clutch-based model, migration occurs towards areas of 'optimal stiffness', where cells can generate maximal traction. In agreement with this model, negative durotaxis is selectively disrupted and even reversed by the partial inhibition of actomyosin contractility. Conversely, positive durotaxis can be switched to negative by lowering the optimal stiffness by the downregulation of talin-a key clutch component. Our results identify the molecular mechanism driving context-dependent positive or negative durotaxis, determined by a cell's contractile and adhesive machinery.
Directed cell movement known as durotaxis, typically associated with cellular migration in response to a substrate gradient of increasing stiffness, is now shown to also occur in the opposite direction, following a gradient of decreasing stiffness.How cells sense tissue stiffness to guide cell migration is a fundamental question in development, fibrosis and cancer. Although durotaxis-cell migration towards increasing substrate stiffness-is well established, it remains unknown whether individual cells can migrate towards softer environments. Here, using microfabricated stiffness gradients, we describe the directed migration of U-251MG glioma cells towards less stiff regions. This 'negative durotaxis' does not coincide with changes in canonical mechanosensitive signalling or actomyosin contractility. Instead, as predicted by the motor-clutch-based model, migration occurs towards areas of 'optimal stiffness', where cells can generate maximal traction. In agreement with this model, negative durotaxis is selectively disrupted and even reversed by the partial inhibition of actomyosin contractility. Conversely, positive durotaxis can be switched to negative by lowering the optimal stiffness by the downregulation of talin-a key clutch component. Our results identify the molecular mechanism driving context-dependent positive or negative durotaxis, determined by a cell's contractile and adhesive machinery.
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