Novel Elastic Devices for the Integration of Chemical and Mechanical Signals in Cells

Mechanosensing is important for many cell activities, including immune response. In-vivo, mechanical and biochemical stimuli collectively regulate cells. However, in-vitro studies could reproduce so far mostly either mechanical or biochemical stimulus alone. Exploring the cooperation of mechanics and biochemistry is crucial for understanding the cellular function.

Here, we developed three experimental platforms that merge mechanical and biochemical stimuli, and used them to study how these stimuli cooperatively regulate the immune function of Natural Killer (NK) cells – lymphocytes of the innate immune system. The first platform consisted of elastomeric surfaces with varied stiffnesses ranging from 50kPa to 3MPa, which were functionalized with activating ligands for NK cells. We found that cell immune response is non-linear with the stiffness, and peaks at 200 kPa. This finding confirms previously hypothesized diversity of mechanotransductive pathways that involve adhesion and activating receptors. The second platform consisted of arrays of elastomeric 300 nm cones functionalized with activating ligands. We found that the cones largely increased the cell immune response comparing to the flat surface, indicating the critical role of the nanotopography in the immune stimulation of NK cells. The third platform consisted of alternating micro-strips with varied stiffness. We found that the strips guide the cell motility and immune response. In overall, our three novel mechanostimulating platforms provides an unprecedented ability to control and regulate incoming mechanical and biochemical signals in cells, and open the pathway to endless experiments aimed at understating the role of these signals in living systems.