Manipulating CD4⁺ T cells by optical tweezers for the initiation of cell-cell transfer of HIV-1

Cell-cell interactions through direct contact are very important for cellular communication and coordination-especially for immune cells. The human immunodeficiency virus type I (HIV-1) induces immune cell interactions between CD4⁺ cells to shuttle between T cells via a virological synapse. A goal to understand the process of cell-cell transmission through virological synapses is to determine the cellular states that allow a chance encounter between cells to become a stable cell-cell adhesion. We demonstrate the use of optical tweezers to manipulate uninfected primary CD4⁺ T cells near HIV Gag-iGFP transfected Jurkat T cells to probe the determinants that induce stable adhesion. When combined with fast 4D confocal fluorescence microscopy, optical tweezers can be utilized not only to facilitate cell-cell contact, but also to simultaneously track the formation of a virological synapse, and ultimately to probe the events that precede virus transfer. HIV-1 infected T cell (green) decorated with uninfected primary T cells (red) by manipulating the primary cells with an optical tweezers system.