(Micro)managing the mechanical microenvironment

Mechanical forces are critical components of the cellular microenvironment and play a pivotal role in driving cellular processes in vivo. Dissecting cellular responses to mechanical forces is challenging, as even simple mechanical stimulation in vitro can cause multiple interdependent changes in the cellular microenvironment. These stimuli include solid deformation, fluid flows, altered physical and chemical surface features, and a complex transfer of loads between the various interacting components of a biological culture system. The active mechanical and biochemical responses of cells to these stimuli in generating internal forces, reorganizing cellular structures, and initiating intracellular signals that specify cell fate and remodel the surrounding environment further complicates cellular response to mechanical forces. Moreover, cells present a non-linear response to combinations of mechanical forces, materials, chemicals, surface features, matrix properties and other effectors. Microtechnology-based approaches to these challenges can yield key insights into the mechanical nature of cellular behaviour, by decoupling stimulation parameters; enabling multimodal control over combinations of stimuli; and increasing experimental throughput to systematically probe cellular response. In this critical review, we briefly discuss the complexities inherent in the mechanical stimulation of cells; survey and critically assess the applications of present microtechnologies in the field of experimental mechanobiology; and explore opportunities and possibilities to use these tools to obtain a deeper understanding of mechanical interactions between cells and their environment.