Abstract

By virtue of recent advances in the technology of the elastic substratum method (ESM) it is now possible to generate accurate vector maps of the traction stresses exerted against a substratum due to the cytoskeletal activity of a single biological cell. We here propose to exploit th ESM so as to answer several fundamental questions about the biological significance of traction stresses, about the physical and molecular origin of these stresses and about the dynamics and control of the cytoskeleton in fibroblasts.
AIM number 1 to test the role of traction in the modalities by which cells sense and respond to mechanical perturbations. This will be accomplished by measuring traction stresses during and following controlled deformations to the substratum.
AIM number 2 to analyze the dynamics of traction, motion and shape in pairs of normal and transformed cells as they come into contact.
AIM number 3 to invent, analyze and test a variety of quantitative mechanical models of the mechanism and molecular origin of the fibroblast-substratum traction stress.
AIM number 4 to test the functional linkage between the transmission to traction forces to the substratum, the presence of various integrin isotypes and the presence of Zxyin containing adhesion sites.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM061806-04
Application #
6646559
Study Section
Special Emphasis Panel (ZRG1-CDF-4 (01))
Program Officer
Flicker, Paula F
Project Start
2000-09-01
Project End
2005-08-31
Budget Start
2003-09-01
Budget End
2005-08-31
Support Year
4
Fiscal Year
2003
Total Cost
$244,844
Indirect Cost

  Institution

Name
Boston University
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
049435266
City
Boston
State
MA
Country
United States
Zip Code
02215

  Publications

Indra, Indrajyoti; Undyala, Vishnu; Kandow, Casey et al. (2011) An in vitro correlation of mechanical forces and metastatic capacity. Phys Biol 8:015015
Undyala, Vishnu V; Dembo, Micah; Cembrola, Katherine et al. (2008) The calpain small subunit regulates cell-substrate mechanical interactions during fibroblast migration. J Cell Sci 121:3581-8
Beningo, Karen A; Hamao, Kozue; Dembo, Micah et al. (2006) Traction forces of fibroblasts are regulated by the Rho-dependent kinase but not by the myosin light chain kinase. Arch Biochem Biophys 456:224-31
Herant, Marc; Heinrich, Volkmar; Dembo, Micah (2005) Mechanics of neutrophil phagocytosis: behavior of the cortical tension. J Cell Sci 118:1789-97
Reinhart-King, Cynthia A; Dembo, Micah; Hammer, Daniel A (2005) The dynamics and mechanics of endothelial cell spreading. Biophys J 89:676-89
Munevar, Steven; Wang, Yu-Li; Dembo, Micah (2004) Regulation of mechanical interactions between fibroblasts and the substratum by stretch-activated Ca2+ entry. J Cell Sci 117:85-92
Curtze, Sami; Dembo, Micah; Miron, Miguel et al. (2004) Dynamic changes in traction forces with DC electric field in osteoblast-like cells. J Cell Sci 117:2721-9
Beningo, Karen A; Dembo, Micah; Wang, Yu-li (2004) Responses of fibroblasts to anchorage of dorsal extracellular matrix receptors. Proc Natl Acad Sci U S A 101:18024-9
Lo, Chun-Min; Buxton, Denis B; Chua, Gregory C H et al. (2004) Nonmuscle myosin IIb is involved in the guidance of fibroblast migration. Mol Biol Cell 15:982-9
Marganski, William A; Dembo, Micah; Wang, Yu-Li (2003) Measurements of cell-generated deformations on flexible substrata using correlation-based optical flow. Methods Enzymol 361:197-211

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