Michael P. Sheetz, Ph.D.
William R Kenan Jr. Professor of Cell Biology and Chair of Biological Sciences, Department of Biological Sciences Associate Professor, Department of Applied Physics and Applied Mathematics.
Mechanical Transduction and Mechanisms of Motility
One critical step in defining cell shape and ultimately the form of the organism is the development of the right force at the right place and time. The shape of organisms, meters in size ultimately relies upon the mechanical properties of cells approximately 30 microns in diameter. Our recent work indicates that direct mechanical effects on cytoskeletal proteins activate force-dependent pathways (Sawada and Sheetz, 2002; Tamada, et al., 2004). Further, protein stretching is a major mechanism for force transduction through substrate priming of tyrosine phosphorylation (Sawada et al., submitted). The coordination of cellular forces depends critically on not only the ability of cells to sense force but also their ability to generate force. We observed recently that the cell force generation on substrates is almost completely the result of myosin II contraction (Cai et al., 2006). Membranes also have mechanical properties that affect cell functions including motility (Dai and Sheetz, 1995; Sheetz 2001) and forces in eukaryotic animal cell membranes are controlled by the adhesion between the membrane and the cytoskeleton through a PIP2-cytoskeleton binding mechanism. The local transduction of force into a biochemical change that can activate global signaling pathways is a critical issue for understanding cellular responses to force and we feel that much of the change comes through direct mechanical effects on cytoskeletal proteins and not through changes in ion channels.
Our studies of the mechanisms of motility have identified 15 to 20 distinct types of motility that appear in many different cells from flies to man (Döbereiner et al., 2006). We originally described the dramatic cell-wide changes from one type of motility to another as phase changes to relate the findings to dramatic changes from one phase of matter to another. Often, only one or two types of motility will be found in a given phase. We are now defining the physical and chemical bases of each step in several types of motility. For example, we observed a periodic type of motility that tests the rigidity and adhesiveness of the substrate (Giannone et al., 2004 and submitted). This type of motility is similar to ruffling and the steps in the process include actin filament assembly in two layers, adhesion site formation, myosin filament assembly between adhesion sites that then pulls on the actin to bend the lamellipodial actin or produce a ruffle. Another type of motility is involved in moving single collagen fibers and it is dependent upon a specific myosin subtype, Myosin IIB (Meshel and Sheetz, 2005). We are expanding the detailed descriptions of these and other types of motility to enable an understanding of complex motility processes that utilize several different types of motility.
Background and Education
Michael Sheetz is the Kenan Professor of Cell Biology and chair of biological sciences, and P.I. for the Nanomedicine Center for Mechanical Biology. Dr. Sheetz received his Ph.D. in chemistry from Caltech, and worked as a postdoctoral fellow at University of California, San Diego, with Professor S. J. Singer. After starting at University of Connecticut Health Center, he moved to Washington University Medical School. In 1990, he became chair of cell biology at Duke Medical Center and moved to Columbia University in 2000.
Honors and Awards
2004 L.L.M. van Deenen Prize in Membrane Biology
Dai J, Sheetz MP.
Choquet D, Felsenfeld DP, Sheetz MP.
Galbraith CG, Sheetz MP.
Sawada Y, Sheetz MP.
Galbraith CG, Yamada KM, Sheetz MP.
Jiang G, Giannone G, Critchley DR, Fukumoto E, Sheetz MP.
Giannone G, Dubin-Thaler BJ, Dobereiner HG, Kieffer N, Bresnick AR, Sheetz MP.
Tamada M, Sheetz MP, Sawada Y.
Meshel AS, Wei Q, Adelstein RS, Sheetz MP.
Vogel V, Sheetz M.
Döbereiner HG, Dubin-Thaler BJ, Hofman JM, Xenius HS, Sims TN, Giannone G, Dustin MI, Wiggins C, Sheetz MP.