Mechanotransductive Materials for Remote Modulation of Cell Signaling

Nearly every cell in the body possesses a mechanism to transduce mechanical force into a biochemical signaling cascade. This suggests that mechanotransductive materials, materials designed to exert a mechanical force of controllable magnitude, have the potential to remotely control cell signaling and downstream function in diverse types of tissue. Recent advances have shown that neuronal activity can be remotely controlled with mechanical force, but the overwhelming majority of cells in the body which are not neurons remain comparatively underexplored in this context. Here, we report results demonstrating two different classes of mechanotransductive nanomaterials that can be used to drive cell signaling across several <i>in vitro</i> and <i>in vivo</i> model systems. Our results show that both small molecule-based, light-activated molecular motors (MMs) and larger (~200 nm) magnetically activated magnetite nanodiscs (MNDs) can drive calcium transients even in non-excitable HEK293T cells without the introduction of a mechanoreceptor transgene. MMs rotate in the MHz frequency regime upon activation with visible light. Similarly, MNDs align themselves with externally applied magnetic field, an effect which can be leveraged to exert torque on their surroundings using a quasistatic, low frequency alternating magnetic field. The calcium transients elicited by these systems receive slightly different contributions from intracellular and extracellular calcium in a manner that suggests a dependence on the localization of the transducer. Further, our results demonstrate that mechanically elicited calcium waves can initiate distinct downstream effects depending on the available protein machinery in the activated tissue. In cardiac myocytes and the cnidarian organism <i>Hydra vulgaris</i>, the calcium transients induced by MM drive action potential firing and muscle contraction. In hippocampal glia and immune cells, MNDs drive intracellular and store-operated calcium signaling cascades. Future work aims to identify additional downstream signaling events activated by mechanical stimulation. These results reveal cell populations amenable to remote mechanical modulation and inform the design of tools to study and control calcium signaling in unexplored systems.