Natural Killer Cell-Mediated Tumor Surveillance: Correlation Between Killing Efficiency, Transient Migration Behavior And Morphology

We recently developed a simple method for automatic characterization of transient migration behavior of natural killer (NK) cells imaged by fluorescence time-lapse microscopy [1]. For imaging we used a microchip-based assay where small numbers of NK and tumor target cells were confined inside microwells. Single-cell tracking revealed differences between NK cells as well as transient changes in migration behavior for individual NK cells. Frequently, NK cells were found to have periods of high motility, interrupted by periods of slow migration or complete stops. Such transient migration arrest periods (TMAPs) often coincided with formation of immune synapses with target cells, but NK cells were also observed to stop spontaneous and prior to cell division or death. To objectively characterize NK cell migration, we used a sliding window approach to evaluate local migration coefficients and mean squared displacement curvature in individual cell trajectories. Three modes of migration were distinguished: TMAPs, directed migration and random movement. Here, we correlated transient migration behavior with NK cell morphology. In general, NK cells were more circular during immune synapse formation and in TMAPs compared to when in directed migration or random movement. On the other hand, motile NK cells had bigger areas and perimeters compared to NK cells engaged in immune synapses or in TMAPs. The method presented can quickly and quantitatively assess migration and morphological properties of different cell populations. Current analysis is focused on determining whether particularly cytotoxic NK cells (serial killers) display distinct properties from other subpopulations of NK cells. 1. Khorshidi, M.A., et al., Analysis of transient migration behavior of natural killer cells imaged in situ and in vitro. Integr Biol (Camb), 2011. 3(7): p. 770-8.