Mechanical communication in fibrosis progression

Mechanical hallmarks of fibrotic microenvironments are both outcomes and causes of fibrosis progression. Understanding how cells sense and transmit mechanical cues in the interplay with extracellular matrix (ECM) and hemodynamic forces is a significant challenge. Recent advances highlight the evolvement of intracellular mechanotransduction pathways responding to ECM remodeling and abnormal hemodynamics (i.e., low and disturbed shear stress, pathological stretch, and increased pressure), which are prevalent biomechanical characteristics of fibrosis in multiple organs (e.g., liver, lung, and heart). Here, we envisage the mechanical communication in cell- ECM, cell-hemodynamics and cell-ECM-cell crosstalk (namely paratensile signaling) during fibrosis expansion. We also provide a comprehensive overview of in vitro and in silico engineering systems for disease modeling that will aid the identification and prediction of mechano-based therapeutic targets to ameliorate fibrosis progression.

Automated summary

The mechanical hallmarks of fibrotic microenvironments are both outcomes and causes of fibrosis progression, presenting a significant challenge in understanding how cells sense and transmit mechanical cues. Advances in intracellular mechanotransduction pathways responding to ECM remodeling and abnormal hemodynamics have been highlighted, providing insights into potential mechano-based therapeutic targets for ameliorating fibrosis progression.