Conference Lecture
Date: Wednesday, 3 December 2008
Time: 08:45 - 09:30 hrs
Venue: Level 2, Theatre
Prof Michael SHEETZ
Professor William R Kenan Jr.
Columbia University
Title: Shaping Cells by Force and Rigidity through Protein Stretching
Control of cell morphology involves the integration of mechanical sensing and cell motility to produce the desired shape of the organism1. Overall, cell traction forces are primarily dependent upon myosin II2. Long term matrix forces appear to be sensed by protein unfolding. One example, is the scaffolding protein, p130Cas, that has a central substrate domain with 15 tyrosines. Active c-Src phosphorylates stretched p130Cas at least 7-fold faster than native, indicating that stretch is the major factor controlling the level of phosphorylation3. Another mode of stretch-dependent protein sensing of force is through the exposure of binding domains by stretch. In the case of talin, stretching of the protein rod domains exposes alpha helices that can then bind to vinculin. Experimentally, we have found that the application of 12 pN of force on a talin rod portion can increase the number of bound vinculin molecules from one to three4. Thus, cytoskeleton protein stretching is a major mechanism by which force can be transduced into tyrosine phosphorylation cascades or focal adhesion protein binding.
1 V. Vogel and M. Sheetz, Nat Rev Mol Cell Biol 7 (4), 265 (2006).
2 Y. Cai, N. Biais, G. Giannone et al., Biophys J 91 (10), 3907 (2006).
3 Y. Sawada, M. Tamada, B. J. Dubin-Thaler et al., Cell 127 (5), 1015 (2006).
4 A. del Rio, R. Perez-Jimenez, R. Liu2, P. Roca-Cusachs, J.M. Fernandez and M.P. Sheetz, submitted.
