Mechanics, signal transduction and effector functions of immune cells

2-sCell to cell and cell-surface interactions play a key role in the function of immune cells. Through ligand recognition and cytoskeleton deformations, living cells exert and support mechanical forces, essential to sense their surrounding environment and develop a specific and adequate response. The capacity of living cells to integrate and evaluate mechanical signals is called mechanotransduction and its understanding is a major current challenge in cell biology, biophysics and immunology. In addition, the translation of mechanical stimuli into effector functions remains largely unknown.

We aim at dissecting mechanotransduction phenomena and its influence on immune cell effector functions, at the single cell scale by combining various approaches: engineered substrates to control cell-surface interaction, innovative surface microscopies, force-based biophysical techniques (atomic force microscopy, optical tweezers, micromanipulations, biomembrane force probe, flow chamber) to exert and record forces on cells. Coupling these techniques to optical microscopy and immunological assays allows us to specifically and quantitatively measure effector cell function such as calcium influx and cytokine production.

Combining these methods we aim at deciphering (i) the state of activation of immune cells (ii) the mechanical organization of healthy and pathological cells (iii) the effector immune response of cells under different mechanical stimuli and (iv) the interplay of mechanics and signaling at cell-surface or cell-cell contacts.