Quantifying shapes and dynamics of migrating T cells in 3D

T cells of the adaptive immune system use sophisticated shape dynamics to migrate towards and neutralize infected and cancerous cells. However, there is still limited quantitative understanding of the migration process in 3D extracellular matrices and across timescales. Here, we leverage recent advances in lattice light sheet microscopy for providing 3D videos at high spatiotemporal resolution to quantitatively explore the shape dynamics of migrating T cell in an unsupervised manner. We first develop a new shape descriptor based on spherical harmonics, and find that, despite any obvious constraints, the shape space of T cells is low dimensional with dynamics organized in ~50s 'motifs'. Using multi-scale wavelet analysis we show that these form a continuum, albeit with some frequently repeated ('stereotyped') motifs. Finally, we connect both shape and the organization of shape dynamic motifs to lab-frame behaviors such as 'turning', and put these in the context of previously established larger-scale migration modes. Our findings may improve the precision of therapeutic development, enable the comparison of T cell migration across different conditions (e.g. tissues, drugs and cell mutants), and more broadly stimulate discussion between researchers in animal and cell behavior.