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.
Wu, J., C.H. Yu, S. Li, B. Zou, Y. Liu, X. Zhu, Y. Guo, H. Xu, W. Zhang, L. Zhang, B. Liu, D. Tian, W. Huang, M.P. Sheetz, and F. Huo. 2015. Parallel near-field photolithography with metal-coated elastomeric masks. Langmuir : the ACS journal of surfaces and colloids. 31:1210-1217.
Yan, J., M. Yao, B.T. Goult, and M.P. Sheetz. 2015. Talin Dependent Mechanosensitivity of Cell Focal Adhesions. Cellular and molecular bioengineering. 8:151-159.
Cui, Y., F.M. Hameed, B. Yang, K. Lee, C.Q. Pan, S. Park, and M. Sheetz. 2015. Cyclic stretching of soft substrates induces spreading and growth. Nature communications. 6:6333.
Iskratsch, T., H. Wolfenson, and M.P. Sheetz. 2014. Appreciating force and shape – the rise of mechanotransduction in cell biology. Nat Rev Mol Cell Biol. 15:825-833.
Iskratsch, T., C.H. Yu, A. Mathur, S. Liu, V. Stevenin, J. Dwyer, J. Hone, E. Ehler, and M. Sheetz. 2013. FHOD1 Is Needed for Directed Forces and Adhesion Maturation during Cell Spreading and Migration. Dev Cell. 27:545-559.
Lynch, C.D., A.M. Lazar, T. Iskratsch, X. Zhang, and M.P. Sheetz. 2013. Endoplasmic spreading requires coalescence of vimentin intermediate filaments at force-bearing adhesions. Mol Biol Cell. 24:21-30.
Roca-Cusachs, P., A. del Rio, E. Puklin-Faucher, N.C. Gauthier, N. Biais, and M.P. Sheetz. 2013. Integrin-dependent force transmission to the extracellular matrix by alpha-actinin triggers adhesion maturation. Proc Natl Acad Sci U S A. 110:E1361-1370.
Luo, W., C.H. Yu, Z.Z. Lieu, J. Allard, A. Mogilner, M.P. Sheetz, and A.D. Bershadsky. 2013. Analysis of the local organization and dynamics of cellular actin networks. J Cell Biol. 202:1057-1073.
Ankam, S., M. Suryana, L.Y. Chan, A.A. Moe, B.K. Teo, J.B. Law, M.P. Sheetz, H.Y. Low, and E.K. Yim. 2013. Substrate topography and size determine the fate of human embryonic stem cells to neuronal or glial lineage. Acta biomaterialia. 9:4535-4545.
Gupta, P., N.C. Gauthier, Y. Cheng-Han, Y. Zuanning, B. Pontes, M. Ohmstede, R. Martin, H.J. Knolker, H.G. Dobereiner, M. Krendel, and M. Sheetz. 2013. Myosin 1E localizes to actin polymerization sites in lamellipodia, affecting actin dynamics and adhesion formation. Biology open. 2:1288-1299.
Higuchi, S., Q. Lin, J. Wang, T.K. Lim, S.B. Joshi, G.S. Anand, M.C. Chung, M.P. Sheetz, and H. Fujita. 2013. Heart extracellular matrix supports cardiomyocyte differentiation of mouse embryonic stem cells. Journal of bioscience and bioengineering. 115:320-325.
Anon, E., X. Serra-Picamal, P. Hersen, N.C. Gauthier, M.P. Sheetz, X. Trepat, and B. Ladoux. 2012. Cell crawling mediates collective cell migration to close undamaged epithelial gaps. Proc Natl Acad Sci U S A. 109:10891-10896.
Mathur, A., S.W. Moore, M.P. Sheetz, and J. Hone. 2012. The role of feature curvature in contact guidance. Acta biomaterialia. 8:2595-2601.
Ghassemi, S., G. Meacci, S. Liu, A.A. Gondarenko, A. Mathur, P. Roca-Cusachs, M.P. Sheetz, and J. Hone. 2012. Cells test substrate rigidity by local contractions on submicrometer pillars. Proc Natl Acad Sci U S A. 109:5328-5333.
Gauthier, N.C., M.A. Fardin, P. Roca-Cusachs, and M.P. Sheetz. 2011. Temporary increase in plasma membrane tension coordinates the activation of exocytosis and contraction during cell spreading. Proc Natl Acad Sci U S A. 108:14467-14472.
Lynch, C.D., N.C. Gauthier, N. Biais, A.M. Lazar, P. Roca-Cusachs, C.H. Yu, and M.P. Sheetz. 2011. Filamin depletion blocks endoplasmic spreading and destabilizes force-bearing adhesions. Mol Biol Cell. 22:1263-1273.
Margadant, F., L.L. Chew, X. Hu, H. Yu, N. Bate, X. Zhang, and M. Sheetz. 2011. Mechanotransduction in vivo by repeated talin stretch-relaxation events depends upon vinculin. PLoS biology. 9:e1001223.
Schvartzman, M., M. Palma, J. Sable, J. Abramson, X. Hu, M.P. Sheetz, and S.J. Wind. 2011. Nanolithographic control of the spatial organization of cellular adhesion receptors at the single-molecule level. Nano letters. 11:1306-1312.