Reciprocity of Cell Mechanics with Extracellular Stimuli: Emerging Opportunities for Translational Medicine

Human cells encounter dynamic mechanical cues in healthy and diseased tissues, which regulate their molecular and biophysical phenotype, including intracellular mechanics as well as force generation. Recent developments in bio/nanomaterials and microfluidics permit exquisitely sensitive measurements of cell mechanics, as well as spatiotemporal control over external mechanical stimuli to regulate cell behavior. In this review, the mechanobiology of cells interacting bidirectionally with their surrounding microenvironment, and the potential relevance for translational medicine are considered. Key fundamental concepts underlying the mechanics of living cells as well as the extracelluar matrix are first introduced. Then the authors consider case studies based on 1) microfluidic measurements of nonadherent cell deformability, 2) cell migration on micro/nano-topographies, 3) traction measurements of cells in three-dimensional (3D) matrix, 4) mechanical programming of organoid morphogenesis, as well as 5) active mechanical stimuli for potential therapeutics. These examples highlight the promise of disease diagnosis using mechanical measurements, a systems-level understanding linking molecular with biophysical phenotype, as well as therapies based on mechanical perturbations. This review concludes with a critical discussion of these emerging technologies and future directions at the interface of engineering, biology, and medicine.