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The Mechanics of Cell Migration and the Cytoskeleton

Juan Carlos del Alamo Mechanical and Aerospace Engineering DepartmentUniversity of California at San DiegoSan Diego, CA Motility of eukaryotic cells is essential for many biological processes such as embryonic development or tissue renewal, as well as for the function of the immune and nervous systems. If misregulated, motility plays an important part in diverse diseases such as cancer, osteoporosis, and mental retardation. Cell migration over surfaces is an integrated chemical and physical process involving the cytoskeleton and its mechanical interaction with the substrate through discrete adhesion regions. Precise quantitative knowledge of the bio-physical processes involved in cell migration is limited. Better measurements are needed to ultimately build models with predictive capabilities. The free-living soil amoeba Dictyostelium has proven to be a valuable model system for the investigation of cell motility with extensive similarities to higher eukaryotes in general, and leukocytes in particular. We present an improved force cytometry method and apply it to the analysis of the dynamics of the chemotactic migration of the amoeboid form of Dictyostelium discoideum. Our explicit calculation of the adhesion force field takes into account the finite thickness of the elastic substrate and improves the accuracy and resolution compared to previous methods. This enables us to quantitatively study the differences in the mechanics of the migration of wild-type and mutant cell lines up a chemoattractant gradient. The time evolution of the elastic energy exerted by the crawling cells on their substrate is quasi-periodic and can be used as a simple indicator of the different phases of the cell crawling cycle. We find that the period of the elastic energy cycle correlates strongly with the mean velocity of migration regardless of cell type. Furthermore, we show that when cells adhere to the substrate, the exert opposing pole forces that are orders of magnitude higher than the force required to overcome the resistance from their environment.

Location: Von Kleinsmid Center (VKC) Room 101

Audiences: Everyone Is Invited

Contact: April Mundy