题目：Force of Life: An Underappreciated Essential Feature

报告人：Ning Wang

University of Illinois at Urbana-Champaign, Urbana, IL, USA

时间：2009年7月23日（周四）上午10:00

地点：生命科学与技术学院二楼会议室

报告摘要：

It is well known that mechanical forces greatly influence the growth and form of every tissue and organ in our bodies (1).  Since all living tissues are made of extracellular matrix and living cells, it is logical for the field to focus on how living cells respond to mechanical forces and interact with the extracellular matrix.  Yet little is known about the mechanism by which individual cells sense these mechanical signals and transduce them into changes in intracellular biochemistry and gene expression – a process known as mechanotransduction.  Over the last decade, several models of cellular mechanotransduction have been proposed (2-4).  The common wisdom is that when a physical force is applied to the cell surface, it distorts the membrane and then quickly dissipates inside the cytoplasm; hence, mechanochemical conversion must only occur in or near these sites on the plasma membrane of the cell surface, followed by diffusion and translocation-based processes, similar to signal transduction after binding of soluble growth factors to their receptors.  As expected, surface membrane receptors, such as integrins, that mediate cell adhesion to extracellular matrix scaffolds, are now recognized to play a central role in mechanotransduction (5).  However, recent experimental data from our laboratory demonstrate that mechanotransduction at the cell surface is only part of the story.  We have shown that rapid, direct mechanotransduction occurs deep in the cytoplasm, fundamentally different from soluble growth factor induced signal transduction (6, 7).  Applied forces at the plasma membrane could have direct impacts on nuclear protein activity and gene expression (8).  Emerging understandings of biomechanical processes at cellular, molecular, and genomic levels will pave the way for molecular mechanomedicine where mechanics/engineering-based technologies are utilized for improving human health.

References

1.        Discher, D.E., Janmey, P., & Wang, Y.L. Tissue cells feel and respond to the stiffness of their substrate. Science 310, 1139-1143 (2005).

2.        Vogel, V. & Sheetz, M. Local force and geometry sensing regulate cell functions. Nat Rev Mol Cell Biol 7, 265-75 (2006).

3.        Orr, A.W., Helmke, B.P., Blackman, B.R. & Schwartz, M.A. Mechanisms of mechanotransduction. Dev Cell 10, 11-20 (2006).

4.         Chien, S. Mechanotransduction and endothelial cell homeostasis: the wisdom of the cell. Am J Physiol Heart Circ Physiol 292, H1209-24 (2007).

5.        Geiger, B., Spatz, J.P., & Bershadsky, A.D.  Environmental sensing through focal adhesions.  Nat Rev Mol Cell Biol 10, 21-33 (2009).

6.        Na, S., Collin, O., Chowdhury, F., Tay, B., Ouyang, M., Wang, Y., & Wang, N.  Rapid signal transduction in living cells is a unique feature of mechanotransduction.  Proc Nat  Acad  Sci USA.  105, 6626-6631 (2008).

7.        Na, S. & Wang, N.  Application of Fluorescence Resonance Energy Transfer and Magnetic Twisting Cytometry to Quantify Mechano-Chemical Signaling Activities in a Living Cell.  Science Signaling 1, pl1 (2008).

8.         Wang, N., Tytell, J.D., & Ingber, D.E.  Mechanotransduction at a distance: mechanically coupling the extracellular matrix with the nucleus. Nat Rev Mol Cell Biol 10, 75-82 (2009).  

报告人简介：

Ning Wang, ScD, Professor of Mechanical Science and Engineering, Department of Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, 1206 W Green St, Urbana, IL 61801 USA; Phone: (217) 265-0913; Fax: (217) 333-1942; Email: nwangrw@uiuc.edu

Ning Wang, ScD, is Full Professor (with tenure) of Mechanical Science and Engineering, in the Department of Mechanical Science and Engineering at University of Illinois at Urbana-Champaign (UIUC). Dr. Wang received his B.S. and M.S. degrees in biomechanics in 1982 and 1984 from Huazhong University of Science and Technology in Wuhan, Hubei, PR China, and the Doctor of Science (ScD) degree in Physiology from Harvard University in 1990.  Dr. Wang did his postdoctoral training at Harvard Medical School and Children’s Hospital from 1991 to 1994.  Dr. Wang became Assistant Professor of Physiology and Cell Biology at Harvard School of Public Health from 1994 to 2000 and Associate Professor of Physiology and Cell Biology from 2000 to 2005 and Senior Lecturer in Physiology and Cell Biology from 2005 to Feb 2006.  Dr. Wang joined the faculty of Mechanical Science and Engineering at UIUC in March 2006. 

Dr. Wang received American Physiological Society Scholander Award in 1991 for his contribution to the understanding of comparative physiology.  Dr. Wang was a visiting professor at University of Paris XII in 1994 and a visiting professor at Huazhong University of Science and Technology since 1994. 

Dr. Wang is a pioneer in cell and molecular mechanics for ~20 years.  Dr. Wang has authored over 80 publications in the field of cell mechanics and mechanotransduction and a number of patents.  Dr. Wang’s primary research interests are on the roles of mechanical forces in controlling and regulating living cell functions.  He co-developed the magnetic twisting cytometry technology for probing living cells’ mechanical properties.  He discovered in 1993 that integrins are mechanosensors.  His lab also developed the three-dimensional magnetic twisting cytometry technology for quantifying mechanical anisotropic signaling in the cytoplasm and the intracellular stress tomography technology for mapping stress propagation inside the cytoplasm and the nucleus of a living cell.  Dr. Wang’s lab has provided experimental evidence that the cytoskeletal prestress dictates a living cell’s shape stability (i.e., shear stiffness), influences gene expression, and regulates stress propagation in the cytoplasm.  Dr. Wang’s lab recently made significant advances in mechanisms of mechanotransduction.  These findings challenge existing classical continuum mechanics “axiom of neighborhood” and the dogma in the field of cell mechanics and cell biology that any applied local mechanical forces cause only local deformation.  These findings may have implications in understanding how living cells integrate mechanical signaling with growth factor signaling.

Currently SCI citations of Dr. Wang’s papers are 4,542 (average citations per article: 70.97) and the H-index of Dr. Wang is 32.

Dr. Ning Wang’s 10 most significant, peer-reviewed, original papers: