Current status and future direction of mechanotransduction mechanisms: Perspectives from cell membrane to nucleus

Mechanical stimuli are widely present in both in vivo and in vitro environments, and studies have shown that these mechanical stimuli can significantly modulate cell fate and regulate physiological or pathological processes such as embryonic development and tumor metastasis. Cells have abundant biomechanical signaling pathways, which can be mainly divided into three types of pathways: cell membrane (integrins, ion channels), cytoplasm (cytoskeleton), and nucleus (nuclear pore complexes, chromatin epigenetic alterations). Through the above-mentioned outside-in and inside-out signaling axes, the cells can accurately perceive the mechanical changes in the microenvironment and make adaptive changes. Despite recent advances in techniques such as linear polarization modulation and cross-scale studies-spanning from organs to cells and molecules, challenges persist in achieving a deeper understanding of cross-scale linkages in mechanotransduction. In this review, we summarize the research progress about the mechanotransduction mechanisms, identify existing gaps, and explore the challenges and future directions in the field. This review aims to provide a solid foundation for understanding the role of biomechanics in physiological states and inspire innovative approaches for its future application in biomedicine.