Multiscale biomechanics and mechanotransduction from liver fibrosis to cancer

A growing body of multiscale biomechanical studies has been proposed to highlight the mechanical cues in the development of hepatic fibrosis and cancer. At the cellular level, changes in mechanical microenvironment induce phenotypic and functional alterations of hepatic cells, initiating a positive feedback loop that promotes liver fibrogenesis and hepatocarcinogenesis. Tumor mechanical microenvironment of hepatocellular carcinoma facilitates tumor cell growth and metastasis, and hinders the drug delivery and immunotherapy. At the molecular level, mechanical forces are sensed and transmitted into hepatic cells via allosteric activation of mechanoreceptors on the cell membrane, leading to the activation of various mechanotransduction pathways including integrin and YAP signaling and then regulating cell function. Thus, the application of mechanomedicine concept in the treatment of liver diseases is promising for rational design and cell-specific delivery of therapeutic drugs. This review mainly discusses the correlation between biomechanical cues and liver diseases from the viewpoint of mechanobiology.