Thursday, November 15, 201210:30 AM - 11:30 AMCNLS Conference Room (TA-3, Bldg 1690)|
Repelling Invasion: Cell Motility and the Immune Defenses
Edward BaniganUniversity of Pennsylvania
The adaptive immune system is responsible for powerful targeted responses to infection and control of chronic disease. It is a critical element of human survival, but many aspects ranging from cell behavior to overall coordination are not well understood. Specific biochemical signals, known as chemokines, play a central role in regulating processes essential to immune function of T cells, which, among other jobs, are responsible for killing invading cells. In order to understand the role of the chemokine CXCL10 during chronic infection by the parasite Toxoplasma gondii, we study the migration statistics of CD8+ T cells in brain tissue. Surprisingly, we find that T cell motility is not described by a Brownian walk, but instead is consistent with a generalized LÚvy walk model consisting of LÚvy-distributed runs alternating with pauses of a LÚvy-distributed duration. Similar to strategies reported for marine predators and other animals, our model predicts that this enables T cells to efficiently locate rare targets. At the cellular level, motility is facilitated through the actin-polymerization machinery within the cell. This machinery rapidly and robustly propels the cell forward through tissue and various obstacles. Through Brownian dynamics simulations, we have shown that polymerization builds up an actin network and concentration gradient that can drive a cell surface forward through repulsive forces. This "self-diffusiophoretic" mechanism is robust against opposing loads and tunable through variation of actin kinetics and the actin-surface interactions. This novel mechanism differs from existing models of cell motility and is generalizable to other cellular and intracellular transport processes.
Host: Bill Hlavacek, T-6 665-1355