Understanding the Collective Chemotactic Behavior of Malignant Lymphocyte Clusters

Single lymphocyte cells under physiological conditions exhibit positive chemotactic migration in response to weak chemical gradients (of the chemokine CCL19) and negative migration (opposing the gradient) in the presence of strong gradients. In contrast, clusters of malignant lymphocytes display positive chemotaxis even when exposed to high chemical gradients. This distinct collective behavior is not well understood and is linked to the increased metastatic potential of lymphocyte clusters over that of individual cells. To understand these cluster dynamics, we develop an agent-based model that incorporates contact inhibition, adhesive interactions, and gradient sensing capabilities. Our analysis reveals that multiple elements contribute to the behavior of these cell clusters. Besides inherent cellular properties such as contact inhibition and gradient sensing, the internal dynamics of the cells are crucial. Specifically, depending on the dynamics of switching from chemoattraction to chemorepulsion and the rate of cell exchanges between the cluster's periphery and interior, clusters can show both chemo-attractive and chemo-repulsive behavior. Insights from our modeling help in understanding the collective behavior of these cells in experiments and can potentially shed light on physiological observations.