Director, Mechanobiology Institute
Distinguished Professor of the Department of Biological Sciences, National University of Singapore
Professor of the Department of Biological Sciences at Columbia University
Cell migration; Cell-cell and cell-substrate interaction
The morphology of cells, organs and whole organisms is determined by the generation of forces on the immediate environment, which is either extracellular matrix or adjacent cells. We are currently engaged in studies to understand the detailed molecular mechanisms involved in a variety of phenomena from cancer metastasis to brain function. Further, we are developing several new tools and protocols for measuring cell forces at the molecular level, which are revealing many new aspects of how cells can both generate and respond to external forces.We have an effort underway to define quantitatively the steps involved in cell adhesion to and spreading on a matrix-coated surface. Using a variety of cell lines that are missing proteins in various motility pathways, we are determining the quantitative changes in the spreading process. This will enable us to generate a detailed model of the process of spreading that will be a model for further studies of how cells differentiate, regenerate tissues or metastasize.
Hailing from Columbia University, Prof Michael Sheetz has more than 40 years’ experience in the biomedical field. Introduced to Singapore by Prof Hew Choy Leong of the National University of Singapore’s Department of Biological Sciences, Prof Sheetz was sought to lead an RCE project. This resulted in a two-year effort to organise and submit a proposal on Mechanobiology where Prof Sheetz set the theme and direction of the Mechanobiology Institute (MBI). As Executive Director of the MBI, he will be spending nine months a year in Singapore to oversee the Institute’s programmes.
Schvartzman, M., Palma, M., Sable, J., Abramson, J., Hu, X., Sheetz, M.P., and Wind, S.J. (2011). Nanolithographic control of the spatial organization of cellular adhesion receptors at the single-molecule level. Nano Lett 11, 1306-1312.
Gauthier, N. C., M. A. Fardin, Roca-Cusachs, P., and Sheetz, M.P. (2011). “Temporary increase in plasma membrane tension coordinates the activation of exocytosis and contraction during cell spreading.” Proc Natl Acad Sci U S A 108(35): 14467-14472.
Margadant, F., L. L. Chew, Hu, X., Yu, H., Bate, N., Zhang, X., Sheetz, M. P. (2011). “Mechanotransduction in Vivo by Repeated Talin Stretch-Relaxation Events Depends Upon Vinculin.” PLoS Biol 9: e1001223.
Yu, C., J. Law, Suryana, M., Low, HY, Sheetz, M. P. (2011). “Early integrin binding to RGD activates actin polymerization and contractile movement that stimulates outward translocation.” Proc Natl Acad Sci U S A 108(51): 20585-20590.
Ghassemi, S., Meacci, G., Liu, S., Gondarenko, A. A., Mathur, A., Roca-Cusachs, P., Sheetz, M. P., Hone, J. (2012). “Cells test substrate rigidity by local contractions on submicrometer pillars.” Proc Natl Acad Sci U S A 109(14): 5328-5333.
Biais, N., B. Ladoux, D. Higashi, M. So, and M. Sheetz. 2008. Cooperative retraction of bundled type IV pili enables nanonewton force generation. PLoS Biol. 6:e87.
Zhang, X., G. Jiang, Y. Cai, S.J. Monkley, D.R. Critchley, and M.P. Sheetz. 2008. Talin depletion reveals independence of initial cell spreading from integrin activation and traction. Nat Cell Biol. 10:1062.
Dubin-Thaler, B.J., J.M. Hofman, Y. Cai, H. Xenias, I. Spielman, A.V. Shneidman, L.A. David, H.G. Dobereiner, C.H. Wiggins, and M.P. Sheetz. 2008. Quantification of cell edge velocities and traction forces reveals distinct motility modules during cell spreading. PLoS ONE. 3:e3735.
del Rio, A., R. Perez-Jimenez, R. Liu, P. Roca-Cusachs, J.M. Fernandez, and M.P. Sheetz. 2009. Stretching single talin rod molecules activates vinculin binding. Science. 323:638-41.