Cell-Matrix Interactions

The extracellular matrix (ECM) choreographs mammalian cell function through a complex array of spatially heterogeneous and dynamic biophysical and biochemical signals. The context in which a cell resides (i.e., cell niche) matters; however, the manner by which cells receive and integrate information from the ECM remains poorly understood and is primarily based on static and two-dimensional cell culture systems. To study ECM regulation of cell function, we have developed user-tunable cell culture systems based on bio-orthogonal chemistries that afford spatiotemporal control over material properties with light.

A specific emphasis of this research has been to dissect how mechanical information is processed by cells during development and disease using photoresponsive hydrogels whose moduli change in a controlled manner with defined light exposure. Using these materials, we have revealed that stem cells possess a 'mechanical memory' - that is stem cell fate is governed not only by the current mechanical environment but also integrates past environments (Nature Materials 2014). We have also highlighted intracellular signaling pathways that regulate stiffness-mediated disease progression in valve calcification (PNAS 2013).



Yang, C.*Tibbitt, M.W.*; Basta, L.; Anseth, K.S. "Reversible and irreversible effects of mechanical dosing on stem cell fateNature Materials201413, 645-652.

Wang, H.; Tibbitt, M.W.; Langer, S.J.; Leinwand, L.A.; Anseth, K.S. "Hydrogels preserve native phenotypes of valvular fibroblasts through an elasticity-regulated PI3K/AKT pathwayProceedings of the National Academy of Sciences2013110, 19336-19341.

Guo, Q.; Wang, X.; Tibbitt, M.W.; Anseth, K.S.; Montell, D.J.; Elisseeff, J.H. "Light activated cell migration in synthetic extracellular matricesBiomaterials201233, 8040-8046.

Tibbitt, M.W.; Kloxin, A.M.; Dyamenahalli, K.U.; Anseth, K.S. "Controlled two-photon photodegradation of PEG hydrogels to study and manipulate subcellular interactions on soft materialsSoft Matter20106, 5100-5108.

Kloxin, A.M.; Tibbitt, M.W.; Kasko, A.M.; Fairbairn, J.A.; Anseth, K.S. "Tunable hydrogels for external manipulation of cellular microenvironments through controlled photodegradationAdvanced Materials201022, 61-66.