Spatio-temporal Patterns of T Cell Traction Forces Depend on Stimulation and Cell Subtype
Mustapha, F., Biarnes-Pelicot, M., Torro, R., El Husseiny, J., Sengupta, K., Puech, P.-H.
T cells exert forces to sense mechano-chemical cues from their target cells. These forces are feeble and are influenced by environmental factors; as a result, they have often been measured under non-physiological stimulation. Furthermore, a full description of the dynamics of force onset is still missing. Here we investigate the early interaction of T cells with specifically activating ultra- soft hydrogels, which mimic target cells with physiologically relevant stiffness of 350-450 Pa. We quantify the dependence of cell spreading and stiffness on gel elasticity, and measure the morphodynamics of early time traction stresses. The time evolution of the strength of traction forces is quantified as the total elastic energy stored in the gel, and the spatial orientation is characterized via the Cauchy stress tensor. We show that T cells generate stresses in distinct spatio-temporal patterns, which can be sorted into 3 categories: random active-noise, localized intermittent-stress, or a sigmoidal energy-time curve arising from a dipole-like spatial pattern which is usually extensile, and rarely contractile. The relative proportion of cells in each category is condition and T cell subtype dependent. The pattern categories likely reflect the way in which the cell interacts with the target via distinct and variously deployed actin-based protrusions. In primary human T cells, the subtype and initial state of the cells strongly impact the relative proportions in each category, in a way that appears coherent with their physiological role. A single metric, which averages the stresses over space and time, fails to capture the stimulation/subtype dependent force application that may be biologically relevant for cell function.
Significance statementThe very first step of acquired immunity depends on recognition of pathogenic peptides by T cells using their special T cell receptors. This process relies on application of forces by the cell, which we measure. These measurements reveal hitherto unknown traction dynamics that is not only ligand and stiffness dependent, but also Primary T cell subtype dependent. We propose mechanisms of force application whereby early filopodia generated feeble forces evolve, depending on condition and cell subtype, into intermittent or sustained lamellipodia generated stress that can be extensile or contractile. We hypothesize that these different modes of force application may be linked to the specific physiology of the T cell subtype.
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