Mechanics of Fibroblast Migration: a Dissertation

摘要: Cell migration involves complex mechanical interactions between cells or and the underlying substrate. Using a newly developed technique, "traction force microscopy", I have been able to visualize dynamic characteristics of forces exerted by migrating fibroblasts such as magnitude, direction, shear. For NIH 3T3 fibroblasts, found that lamellipodium provides nearly all necessary for cell migration. A high shear zone separates from remainder body, suggesting they are mechanically distinct entities. The timing tractions at leading edge, well spatial distribution, bears no apparent relationship concurrent local protrusive activities, yet changes in traction patterns often precede direction. In H-ras transformed isolated regions weak, transient pseudopods along appeared act against one another. resulting pattern suggested there were multiple disorganized domains. These results support frontal towing model where edge served actively pull body forward. cells, weak poorly coordinated coupled with substrate-adhesions likely responsible abnormal motile behavior these cells. To probe beneath various substrate inhibitor (GRGDTP peptide) was locally applied while imaging stress distribution on utilizing microscopy. both spontaneous GRGDTP induced detachment trailing resulted extensive shortening change overall magnitude Conversely, disruption dramatic global loss pnor any significant shortening. transmit their contractile through two types adhesions. Leading adhesions unique ability active propulsive whereas end created passive resistance during readily redistributed loads upon detachment. also investigated how regulate based input. My showed stretching flexible increases intracellular calcium concentration fibroblasts. Treatment gadolinium, known stretch-activated ion channel inhibitor, inhibit without inhibiting cellular spread morphology activities. Gadolinium treatment caused pronounced decrease vinculin phosphotyrosine concentrations focal Local application gadolinium region had detectable effect overall…