Modeling Immune Cell Migration

Cytotoxic T-lymphocytes (CTLs) and natural killer (NK) cells are the killer cells of the immune system and are responsible for the elimination of potential dangers, such as virus-infected and tumor cells. CTLs and NK cells migrate actively within tissues to encounter target cells, and form a tight connection with them called the immunological synapse that enables killing. However, how migration is regulated in these cells for an efficient reach of their target remains a central question in immunology. Here we analyzed the migration of CTLs and NK cells in 2 dimensions in the absence of external cues to mirror the initial immune response where no signals guide killer cells to their target. By calculating the mean square displacement and the velocity autocorrelation we found that CTLs perform a persistent random walk. Furthermore, cell shape analysis enabled us to establish a model for killer cell migration where the movement of the cell is determined by several independent internal “force generators”. Each of them switches between active and inactive states. We found a correlation between the number of the “force generators” and the duration of their activity to the number and life time of lamellipodia. Our numerical simulations revealed that the search time in a given space depends on the behavior of cells upon contact with boundaries. We believe that simulation of migration and search strategy of killer cells will ultimately lead to an improved understanding of the immune response.