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.
Zhang X, Moore SW, Iskratsch T, Sheetz MP: N-Wasp-Directed Actin Polymerization Activates Cas Phosphorylation and Lamellipodium Spreading. J Cell Sci 2014, 127: 1394-405.
Yao M, Goult BT, Chen H, Cong P, Sheetz MP, Yan J: Mechanical Activation of Vinculin Binding to Talin Locks Talin in an Unfolded Conformation. Sci Rep 2014, 4: 4610.
Gupta P, Gauthier NC, Yu CH, Zuanning Y, Pontes B, Ohmstede M, Martin R, Knolker HJ, Dobereiner HG, Krendel M, Sheetz MP: Myosin 1E localizes to actin polymerization sites in lamellipodia, affecting actin dynamics and adhesion formation. Biol Open 2013, 2: 1288-99.
Iskratsch T, Yu CH, Mathur A, Liu S, Stevenin V, Dwyer J, Hone J, Ehler E, Sheetz MP: FHOD1 Is Needed for Directed Forces and Adhesion Maturation during Cell Spreading and Migration. Dev Cell 2013, 27: 545-559.
Higuchi S, Lin Q, Wang J, Lim TK, Joshi SB, Anand GS, Chung MCM, Sheetz MP, Fujita H: Heart extracellular matrix supports cardiomyocyte differentiation of mouse embryonic stem cells. J Biosci Bioeng 2013 115: 320-325.
Lynch CD, Lazar AM, Iskratsch T, Zhang X, Sheetz, MP: Endoplasmic spreading requires coalescence of vimentin intermediate filaments at force-bearing adhesions. Mol Biol Cell 2013, 24: 21-30.
Roca-Cusachs P, del Rio A, Puklin-Faucher E, Gauthier NC, Biais N, Sheetz, MP: Integrin-dependent force transmission to the extracellular matrix by alpha-actinin triggers adhesion maturation. PNAS 2013, 110: E1361-E1370.
Yu, CH, Rafiq NBM, Krishnasamy A, Hartman KL, Jones GE, Bershadsky AD, Sheetz MP: Integrin-Matrix Clusters Form Podosome-like Adhesions in the Absence of Traction Forces. Cell Rep 2013, 5: 1456-1468.
Luo W, Yu CH, Lieu ZZ, Allard J, Mogilner A, Sheetz, MP, Bershadsky AD: Analysis of the local organization and dynamics of cellular actin networks. J Cell Biol 2013, 202: 1057-1073.
Ghassemi S, Meacci G, Liu S, Gondarenko AA, Mathur A, Roca-Cusachs P, Sheetz MP, Hone J: Cells Test Substrate Rigidity by Local Contractions on Submicrometer Pillars. PNAS 2012, 109: 5328-5333.
Roca-Cusachs P, Iskratsch T, Sheetz MP: Finding the Weakest Link – Exploring Integrin-Mediated Mechanical Molecular Pathways. J Cell Sci 2012, 125: 3025-3038.
Sheetz, MP: Following Nature’s Challenges. Nat Med 2012, 18: 1483-1485.
Yim EKF, Sheetz MP: Force-Dependent Cell Signaling in Stem Cell Differentiation. Stem Cell Res Ther 2012, 3.
Gauthier NC, Masters TA, Sheetz MP: Mechanical Feedback between Membrane Tension and Dynamics. Trends Cell Biol 2012, 22: 527-535.
Yu CH, Luo W, Sheetz MP: Spatial-Temporal Reorganization of Activated Integrins. Cell Adh Migr 2012, 6: 280-284.
Moe AAK, Suryana M, Marcy G, Lim SK, Ankam S, Goh JZW, Jin J, Teo BKK, Law JBK, Low HY, Goh ELK, Sheetz MP, Yim EKF: Microarray with Micro- and Nano-Topographies Enables Identification of the Optimal Topography for Directing the Differentiation of Primary Murine Neural Progenitor Cells. Small 2012, 8: 3050-3061.
Pan CQ, Sudol M, Sheetz MP, Low BC: Modularity and Functional Plasticity of Scaffold Proteins as P(L)Acemakers in Cell Signaling. Cell Sig 2012, 24: 2143-2165.