Cell-matrix mechanobiology
Cells sense the mechanical properties of their surrounding extracellular matrix (ECM), including elasticity, viscoelasticity, and plasticity, and this mechanosensing regulates cell fate during development and disease. While cells are typically assumed to sense ECM mechanics through direct adhesive interactions, many biomedically important cells such as mesenchymal stem cells, chondrocytes, and cancer cells rapidly secrete their own “nascent” matrix that occupies the cell-ECM interface, raising questions as to how these cells can sense the mechanical properties of the ECM. As a postdoc in the Chaudhuri lab at Stanford, I investigated this problem and studied how chondrocytes sense and respond to hydrogel ECMs with tunable elastic, viscoelastic, and plastic properties.
In my study [1], I showed that hydrogel rheological properties mediate the accumulation of the nascent matrix at the cell-hydrogel interface. I showed that viscoelastic and plastic hydrogels facilitate the penetration of the nascent matrix into the surrounding network, while elastic hydrogels confine the nascent matrix in the pericellular space, thus imposing solid stress on the cells. This solid stress drives an osteoarthritis- and injury-like response in chondrocytes, characterized by NF-kB-driven inflammation, co-activation of anabolism and catabolism, and a striking chondroprogenitor-like migratory behavior within the hydrogel. I examined these confined migration events in detail, and found that chondrocytes leverage mitosis as a propulsive mechanism to breach their confining matrix and escape solid stress. These findings show that matrix-secreting cells sense the solid stress arising from nascent matrix confinement within the ECM – which is regulated by the rheological properties of the ECM – and establishes solid stress as a mechanobiological framework for understanding cartilage osteoarthritis and injury.
Summary illustration of how hydrogel rheological properties regulate the confinement of the nascent matrix, which imposes solid stress on chondrocytes, and drives an osteoarthritis- and injury-like response characterized by inflammation and migration. Taken from Song et al., [1].
- Song, J., Loveland, S., Yang, F., Bhutani, N., Levenston, M. E., & Chaudhuri, O. “Hydrogel confinement of the secreted nascent matrix imposes solid stress and mediates pathology of chondrocytes.” bioRxiv. (2026)