Striated muscle diseases lead to progressive changes in cellular and tissue mechanics. These changes contribute to degeneration, inflammation, impaired regeneration, and fibrosis. Although mechanical dysfunction is recognized as a key driver of pathological signaling, the use of quantitative mechanical phenotyping in muscle disease research remains limited. This limitation is primarily due to the lack of accessible and scalable measurement technologies.
In this context, we emphasize nanoindentation as a versatile and quantitative method for probing disease-relevant mechanics in striated muscle. We review representative, peer-reviewed studies that demonstrate how nanoindentation facilitates robust mechanical measurements capturing key mechanopathological features of dystrophy and cardiomyopathy. Specifically, we illustrate the bio-indenter’s ability to measure: (i) cytoskeletal remodeling, (ii) mechanical interactions between cells and ECM, and (iii) fibrosis-related changes.
Published studies reveal increased cellular stiffness associated with cytoskeletal remodeling—such as microtubule densification and altered tubulin acetylation—which negatively impacts contractility and mechanotransduction. This approach also captures disease- and age-related changes in mechanosensitivity in muscle stem cells, where reduced adhesion strength, altered morphology, and diminished mechanical responses correlate with impaired regenerative capacity and sarcopenia .
Furthermore, nanoindentation identifies fibrotic activation through measurements of single-cell stiffening and viscoelastic properties in human atrial and cardiac fibroblasts. Published data demonstrate that effective Young’s modulus and time-dependent mechanical parameters link fibroblast mechanophenotypes to the progression of fibrosis and the effects of pharmacological modulation, supporting the idea of mechanical properties as quantitative biomarkers of fibrosis .
Overall, nanoindentation captures stiffness, viscoelasticity, and mechanical heterogeneity as quantitative mechanophenotypes in striated muscle diseases. Our indenters offer a non-destructive, highly localized, and scalable measurement approach that is compatible with standard multi-well plate formats, facilitating the systematic integration of mechanical readouts into disease modeling, therapeutic screening, and regenerative medicine workflows.