Regulation of pseudopodia localization in lymphocytes through application of mechanical forces by optical tweezers

Abstract

T-lymphocytes are responsible for cell-mediated immunity, and recognize antigens on target cells (e.g., tumor cells, virus-infected cells) and antigen presenting cells (e.g., macrophages, dendritic cells). While mechanical forces applied to a cell surface can produce alterations in the cytoskeletal structure, leading to global structural rearrangements and changes in the intracellular biochemistry and gene expression, it remains unknown if local mechanical forces acting at the lymphocyte-antigen interaction site play any role in lymphocyte activation following antigen recognition. In this study we investigate the effect of such forces induced by optical tweezers on the lymphocyte's morphological response. We brought optically trapped polystyrene beads, coated with a specific antibody against a clonotypic epitope of the T-cell receptors (TCRs), in contact with individual lymphocytes and applied mechanical forces at the TCR-antibody interaction site. Although bead size was a factor, simple bead contact tended to induce formation of pseudopodia that appeared randomly over the cell's surface, while application of tangential forces at the interaction site redirected pseudopodia formation toward that site and promoted endocytosis activity. We propose that local forces play a key role in the initial lymphocyte adhesion to antigen-bearing cells, and may be implicated in antigen-specific motility, transendothelial migration, and tissue homing to sites of inflammation.