Mechanical Signaling: Molecular Mechanisms, Biological Functions, Diseases, and Therapeutic Targets

ABSTRACT Cell mechanics is a fundamental regulator of numerous cellular processes, orchestrating critical biological activities spanning from embryogenesis to senescence. Cells continuously sense and respond to mechanical cues through specialized interactions between membrane‐bound adhesion proteins, such as integrins, and adhesive ligands within the extracellular matrix (ECM). This bidirectional interaction forms the basis of mechanotransduction—a complex, dynamic process that ultimately leads to alterations in nuclear mechanics and governs essential cellular functions, including migration, tissue morphogenesis, and so on. In this review, we provide an overview of these dynamic cell–ECM interactions and delve into the intricate molecular mechanisms underlying mechanotransduction. We further introduce advanced research methodologies and emerging clinical tools used to investigate cellular mechanical phenotype, mechanotransduction, and diseases progression. In addition, we analyzed the roles of mechanical biomarkers in the development and progression of cancer, fibrosis, and aging. We highlighted the necessity of drug development targeting mechanotransduction, providing examples of drugs that have already entered clinical trials and preclinical tools. By integrating current findings and outlining emerging perspectives, this review aims to provide critical insights and inspire future efforts in understanding, manipulating, and clinically exploiting mechanotransduction‐targeted markers to regulate the progression of diseases such as cancer, fibrosis, and aging.