Adhesion gateway: decoding mechanobiological cues for cytoskeletal reconfiguration

Cellular adhesion is a central determinant of functional three-dimensional tissue structures. The challenges lie in restoring stable cell-to-cell and cell-to-matrix adhesion from dissociated cells without compromising cell integrity and impairing the ability of cells to form functional 3D structures. Recent breakthroughs have elucidated diverse, force-sensitive mechanisms for inducing cellular adhesion, providing a foundation for advanced therapeutic and engineering applications. This review provides a comprehensive analysis of recent work on individual mechanosensing and mechanotransduction pathways governing cellular adhesion. Collectively, we integrate several mechanical stimulation strategies, chemotransduction, adhesion-associated molecular networks, and AFM-based quantitative methodologies into a unified framework centered on the experimental toolbox used in adhesion mechanobiology. We further encompass the full spectrum of mechanobiology, starting from various mechanobiological cues (such as mechanical stimuli, micropatterning, stretch-induced adhesion, and biochemical strategies) and the role of molecular players (like integrin, vinculin, talin, actin, cadherin, and beyond) in focal adhesion. Downstream effects of gene expression, cellular responses to different surface stiffness, and the methodological approaches of bio-atomic force microscopy (Bio-AFM) and diverse modes of external stimulation were highlighted.