The application of cyclic strain is known to enhance myoblast differentiation and muscle growth in vitro and in vivo. However, current techniques apply strain to full tissues or cell monolayers, making it difficult to evaluate whether mechanical stimulation at the subcellular or single-cell scales would drive myoblast differentiation. Here, we report the use of optomechanical actuator (OMA) particles, comprised of a ∼0.6 μm responsive hydrogel coating a gold nanorod (100 × 20 nm) core, to mechanically stimulate the integrin receptors in myoblasts. When illuminated with near-infrared (NIR) light, OMA nanoparticles rapidly collapse, exerting mechanical forces to cell receptors bound to immobilized particles. Using a pulsed illumination pattern, we applied cyclic integrin forces to C2C12 myoblasts cultured on a monolayer of OMA particles and then measured the cellular response. We found that 20 min of OMA actuation resulted in cellular elongation in the direction of the stimulus and enhancement of nuclear YAP1 accumulation, an effector of ERK phosphorylation. Cellular response was dependent on direct conjugation of RGD peptides to the OMA particles. Repeated OMA mechanical stimulation for 5 days led to enhanced myogenesis as quantified using cell alignment, fusion, and sarcomeric myosin expression in myotubes. OMA-mediated myogenesis was sensitive to the geometry of stimulation but not to MEK1/2 inhibition. Finally, we found that OMA stimulation in regions proximal to the nucleus resulted in localization of the transcription activator YAP-1 to the nucleus, further suggesting the role of YAP1 in mechanotransduction in C2C12 cells. These findings demonstrate OMAs as a novel tool for studying the role of spatially localized forces in influencing myogenesis.

Hydrogel-based MAMs are the most diverse and intensely studied, and have potential to be programmed with various responding behaviors and have broad applications in areas ranging from biomedical engineering to robotics. Hydrogel programmability, in some literature, refers to the fine-tuning of hydrogel deformation patterns. [4] Other works define programmability of hydrogels as molecular sequencing or arrangement within gel networks. [5] To provide a more consistent overview of programmable hydrogelbased MAMs, this review defines programmability as the ability to tune the input-output response function of the MAMs through either molecular design or patterning of the material across multiple length scales. There are MAMs that are responsive but the response function cannot be easily altered or tuned. For example, a conventional hydrogel can swell and deswell by controlling the humidity. But without spatially patterning the material or without doping certain copolymers into the gel, this type of conventional material is not inherently programmable. We will further discuss the approaches to integrate programmability into MAMs in Section 3.In this review, we first describe the chemical components of hydrogel-based MAMs and their fabrication, followed by specific approaches toward programmability. Then, a detailed classification of responsivity mechanisms is provided, along with discussion of the intimate relationships between material structure and their responsive behaviors. We then end by summarizing current applications of MAMs across multiple disciplines, and the future directions and applications of mechanically responsive hydrogels. Components of HydrogelsMechanical responsivity has been observed in nearly all types of materials both hard and soft materials, spanning from metals to ceramics and polymers. Popular examples include shape-memory metal alloys, [6] piezoelectric ceramics, [7] and thermoresponsive polymers. [8] Herein, we will exlusively discuss programmable MAMs that are primarily composed of polymer hydrogels. This is because hydrogel materials are great candidates for flexible devices and bioengineering studies, and this has inspired multidisciplinary research and numerous potential applications. To be more consistent, inorganic nanoparticles, plastic, rubber, ceramics, polymer micelles/capsules, will not be discussed here since these types of materials are not hydrogels. Programmable mechanically active materials (MAMs) are defined as materials that can sense and transduce external stimuli into mechanical outputs or conversely that can detect mechanical stimuli and respond through an optical change or other change in the appearance of the material. Programmable MAMs are a subset of responsive materials and offer potential in next generation robotics and smart systems. This review specifically focuses on hydrogel-based MAMs because of their mechanical compliance, programmability, biocompatibility, and cost-efficiency. First, the composition of hydrogel MAMs along with the top-down and bottom-up a...