Cells feel the beat – temporal effect of cyclic mechanical actuation on muscle cells

Understanding how muscle cells (myoblasts) react to mechanical actuation with a precise spatio-temporal control is challenging and requires new material systems to achieve a better insights to mechanotransduction pathways involved in myogenic differentiation. Here, we employ a recently developed light-responsive hydrogel as an actuating substrate with native tissue-like modulus to stimulate myoblast cells in the absence of any additional differentiation factors. A near-infrared micro-projection system allows to locally define the actuation frequency and duration and investigate cellular processes of proliferation and differentiation. We observe that actuation enhances cell proliferation and migration, associated with nuclear translocation of myogenic proteins, such as MyoD and Yes-associated protein (YAP). Furthermore, we record a significant reduction of collagen type I and fibronectin deposition, suggesting an antifibrotic effect of the actuation. In conclusion, our findings emphasize the need of controlling the actuation time (training schedule) and amplitude for inducing myoblasts proliferation and mechanotransduction, underling the importance of using a synthetic material system that can be adjusted to support myogenic differentiation and other cell processes in vitro.