Refereed journal article or data article (A1)
Directed cell migration towards softer environments
List of Authors: 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.
Publisher: Nature Portfolio
Publication year: 2022
Journal: Nature Materials
Journal name in source: NATURE MATERIALS
Journal acronym: NAT MATER
Volume number: 21
Start page: 1081
End page: 1090
Number of pages: 17
ISSN: 1476-1122
eISSN: 1476-4660
DOI: http://dx.doi.org/10.1038/s41563-022-01294-2
URL: https://www.nature.com/articles/s41563-022-01294-2
Abstract
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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