Actin-mediated centrosome polarization during immune response in cytotoxic T lymphocytes

Cytotoxic T Lymphocytes (CTLs), an important part of the adaptive immune system, target infected cells by the formation of an immune synapse (IS) at the interface of CTL and target cell. Upon activation, the centrosome in CTLs polarizes towards the IS and helps deliver cytotoxic granules into the target cell via secretion through the actin depleted region of the IS. Most existing theories for the mechanism behind centrosome polarization rely on the microtubule–motor protein (dynein) complex. However, recent experiments suggest that the actin cytoskeleton can also play a large role in the centrosome translocation. Here, we study centrosome polarization mediated by actin polymerization forces by building a minimal model with a 1D channel representing the CTL's cytoplasm. The centrosome is modeled as a finite-sized Brownian Particle placed in a gradient of actin density (modeling actin depletion in the IS region) and is subjected to stochastic forces from asymmetric actin polymerization. We then simulate the centrosome dynamics, measure the time it takes for the centrosome to reach the IS and compare it with timescales obtained from other models like dynein-mediated microtubule pulling, capture-shrinkage mechanisms, as well as from experiments. Our results suggest that actin-mediated centrosome polarization is a viable mechanism for centrosome polarization and that it could act in concert with other motor based mechanisms.