Model of how septin ring compartmentalization aids T-cell circumnavigation in extracellular matrices*

In order to efficiently migrate through complex environments, T cells adopt a variety of migration modes including amoeboid and mesenchymal motions. Their ability to push the nucleus through narrow passages is critical for their migration through the extracellular matrix. Zhovmer et al. recently discovered that T cells in collagen matrices move with the aid of septin rings, which form around the nucleus at locations where extracellular matrix obstacles create high negative cell curvature. The resulting septin/F-actin rings subdivide the volume of the cell into separate compartments, with potentially different microenvironments. We developed a 2D computational model to test how such compartmentalization aids cell motility. In the model, beads representing the plasma membrane and nucleus move according to forces of bending rigidity, tension, contraction, fluctuating protrusions, and excluded volume interactions from encountered obstacles. Cell and nuclear volume conservation are implemented as area conservation forces. A weak nuclear centering force is implemented to represent cytoskeleton- and organelle-mediated nuclear centering. We assume that septin ring formation leads to compartment boundaries at sites where obstacles enforce proximity between the cell membrane and nucleus. We show that formation of these boundaries leads to a nuclear piston mechanism that enhances motility at high obstacle density.