Effects of the manipulation of ligand mobility and geometry on the cytotoxic synapse

SÁNCHEZ M.F.; CARRER, D. C.; GARCÍA-SÁEZ A.J.

Tucumán

Congreso; Reunón III LAFeBS, IX IberoAmerican Congress of Biophysics, XLV SAB; 2016

Cells respond to many external stimuli through membrane receptors. Among the major programmed cell death pathways, Fas mediated apoptosis (extrinsic apoptosis) is one of the most important. The signaling events mediated by Fas receptor have been extensively studied by adding a soluble agonist to the cells culture medium. That is to say, by stimulating the cells in a way that is spatially isotropic. In this work, we utilize receptor Fas activation as a tool to approach a more general question: which is the response of a cell to simuli that are chemically identical but spatially/geometrically/kinetically diverse?To tackle this question we generated functionalized surfaces that simulate the plasma membrane of a cytotoxic T lymphocyte with controlled geometry and fluidity. Our results show that there is a remarkable dependence of the cells apoptotic response with the mobility of the ligand. The response is also dose-dependent. Thus, the spatial distribution and mobility of the stimulus can modulate the apoptotic cell response. Also, the activation of Fas receptor occurs in an anisotropic way, (initially) only in the point of contact between the cell and the artificial membrane, showing a significant difference in both receptor clustering and receptor diffusion in that point in comparison with other parts of the cell membrane.