Single Cell Mechanics in Disease Progression

Mechanical force transmission is essential for maintaining cellular structure and function. Forces generated by the extracellular matrix (ECM) and neighboring cells are transmitted via adhesion and junctional complexes to the cytoskeleton and nucleus, forming an integrated mechanical network. These forces at cell-substrate and cell-cell interfaces can be quantified using biophysical tools such as atomic force microscopy, magnetic tweezers, and Förster resonance energy transfer, which have become core technologies for characterizing cellular mechanical properties. Disruption of cellular mechanical homeostasis underlies diverse pathological conditions: In cancer, cell adhesion loss and cytoskeletal reorganization promote metastasis; in fibrosis, increased ECM stiffness enhances cellular contractility; in inflammation, vascular and epithelial barriers are compromised by junctional breakdown; and in cardiomyopathies and skin-blistering disorders, desmosomal protein defects impair electrical and mechanical coupling. Beyond the cell surface, mechanical forces are transmitted to the nucleus, where they induce lamin-chromatin interactions, lamina-associated domain rearrangement, and heterochromatin condensation, thereby influencing gene expression and cell fate determination. This review aims to summarize the mechanisms of cellular mechanotransduction from the extracellular microenvironment to the nucleus and discusses related diagnostic and therapeutic strategies. A mechanobiological perspective on disease provides valuable insights for developing treatments for cancer, fibrosis, aging, and laminopathies.