Instantaneous distribution of cellular tractions during fibroblast migration

BIOT 381

Zhi Pan, zpan@ic.sunysb.edu1, Yajie Liu2, Kaustabh Ghosh3, Toshio Nakamura2, Richard A. F. Clark4, and Miriam Rafailovich, miriam.rafailovich@sunysb.edu1. (1) Department of Materials Science and Engineering, SUNY at Stony Brook, Stony Brook, NY 11794, (2) Department of Mechanical Engineering, SUNY at Stony Brook, Stony Brook, NY 11794, (3) Harvard Medical School, Harvard University, Boston, MA 02115, (4) Department of Biomedical Engineering,Dermatology and Medicine, SUNY at Stony Brook, Stony Brook, NY 11794
Cellular traction forces are the physical interaction at cell-substrate interface. They are transmitted to the substrate through focal adhesions, which as they assemble and disassemble generate or release traction forces. This is a dynamic process which directly determines where and how fast cells migrate. Therefore, the instantaneous distribution of cellular tractions is critical to measure in order for us to understand the mechanisms of cell migration. However, the complexity of existing methods for traction force calculation is a major limitation to achieving a precise measurement in real time. Here we demonstrated an effective algorithm to quantify the cellular traction distribution on a 2D surface using optical digital image speckle correlation (DISC) technique in combination with finite element method (FEM). We also constructed an extracellular matrix mimic substrate through cross-linking a thiol-functionalized hyaluronan (HA-DTPH) gel with fibronectin functional domains (FNfds). The cell-substrate adhesiveness could then be controlled by the ligand type or density. We observed the migration of human dermal fibroblasts on these matrices and mapped the corresponding traction distribution during their migration. We found that traction gradients between the front and the rear of the cell directly correlate to cell migration speed rather than the adhesion strength or the magnitude of the traction forces across the whole cell. Furthermore, we found that regardless of the magnitude of the traction forces the cells moved with a nearly constant velocity, which appeared in a pulsed manner, where the pulses were of constant magnitude. We were able to explain this phenomenon by observing a reverse traction gradient across the nucleus, which would increase or decrease, depending on the cell velocity. Hence we concluded that fibroblast migration was a discontinuous process, where the cell could opt to exert a “breaking” force around the nucleus to control its velocity.
 

Poster Session
5:30 PM-7:30 PM, Wednesday, August 22, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Biochemical Technology

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007