Invited Talk

Mechanobiology of extracellular matrix fibers in cancer

ETH Zurich, Laboratory of Applied Mechanobiology, Institute of Translational Medicine, Department for Health Sciences and Technology (D-HEST), CH-8093 Zürich, Switzerland

Contact:  | Website

Even though the importance of the tumor microenvironment (TME) in guiding cancer initiation and progression is well recognized, most studies to date have focused on mapping the overall changes in tissue stiffness due to the lack of nanoscale force or tension sensors of the TME. To investigate how the tension of single ECM fibers changes during tumorigenesis, we recently introduced and validated a tension-sensitive peptide probe, which specifically binds with nanomolar affinity to untensed, but not to stretched Fibronectin fibers. We then mapped fibronectin’s fiber tension in tumor mouse models, as well as in human breast carcinomas. Visualizing ECM fiber tension at the molecular level in organ tissues versus cancer is highly significant as changes in ECM fiber tension can regulate the affinity of ECM binding partners by either exposing cryptic binding sites or destroying others. For example, fibronectin’s fiber tension tunes the binding strength of tissue transglutaminase 2, as well as of interleukin-7, and can tune cell adhesion preference from 51 to v3 integrins. A thorough understanding of these physical changes is therefore critical for the development of innovative approaches to cancer therapies.