Refereed journal article or data article (A1)

Directed cell migration towards softer environments

List of AuthorsIsomursu 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.

PublisherNature Portfolio

Publication year2022

JournalNature Materials

Journal name in sourceNATURE MATERIALS

Journal acronymNAT MATER

Volume number21

Start page1081

End page1090

Number of pages17





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.

Last updated on 2023-26-05 at 10:00