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 fate" Nature Materials, 2014, 13, 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 pathway" Proceedings of the National Academy of Sciences, 2013, 110, 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 matrices" Biomaterials, 2012, 33, 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 materials" Soft Matter, 2010, 6, 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 photodegradation" Advanced Materials, 2010, 22, 61-66.