Surfing the Actin Wave: Mathematical Modeling of Natural Killer Cell Synapse Formation

MontanaFerita

University of Utah

"Surfing the Actin Wave: Mathematical Modeling of Natural Killer Cell Synapse Formation"

Natural killer (NK) cells are members of the innate immune system and are proving to be a lethal weapon against cancer. To unlock the full power of NK cells, we must first address the central question: How does an NK cell recognize a malignant cell? To assess a target cell, an NK cell forms an immunological synapse, which is the interaction zone between the two cells. Ligand-receptor binding within the synapse triggers downstream activating and inhibitory signaling pathways that integrate to control the actin cytoskeleton network. Dominating activating signals causes the NK cell’s actin network to reorganize which transports more receptors to the synapse, thereby generating a positive feedback loop. Mechanistically, activating signals lead to the activation of the Arp2/3 complex which creates a branched actin network. In return, the flow of this network drives the centripetal transport of receptors to the synapse. We propose an advection-diffusion model to capture this phenomenon. Furthermore, we test what ligand-receptor densities permit synapse formation.
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