Bio-Nano Devices for Ultra-High Resolution Study of Mechanical Forces in Immune Cells

Lital Mordechay 1,2 Guillaume Le Saux 1,2 Dor Yehuda 1,2 Uzi Hadad 2 Avishay Edri 3 Angel Porgador 3 Mark Schvartzman 1,2
1Ben-Gurion University of the Negev, Israel
2Ben-Gurion University of the Negev, Israel
3Ben-Gurion University of the Negev, Israel

It has been recently established that the immune cells (Cytotoxic lymphocytes - e.g. T cells and Natural Killer (NK) cells) communicate their environment by sensing its mechanical properties. The mechanical sensing of immune cells regulates their important functions, such as adhesion, proliferation, differential, and cytotoxic activity. Today, extensive research is aimed at understanding the cell mechanotransduction. However, this mechanism, especially its nanoscale spatiotemporal nature, is not yet understood due to the lack of experimental tools that are able to resolve cell forces at the nanoscale.

In this work, we developed nanodevices for the study of cellular forces with nanoscale spatial resolution. The devices are based on a surface patterned with elastomeric nanopillars of cylindrical or pyramidal shape, whose their tips are selectively coated with ligands specifically recognized by activating or inhibitory immunoreceptors. This structure allowed to evaluate the role of rigidity of the cell environment, while restricting the cell adhesion on the top of the pillars. We used these devices for the study of NK cell mechanosensing. In particular, we examined the effect of different ligands, as well as the pillar rigidity, on the cell immune activity, and elucidate their influences on NK cells immune response. The outcome of this research is important for understanding the fundamental mechanism of immune system, as well as for establishing novel rationally designed immunotherapeutic approaches.

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