Tissue mechanics and fibrosis

Abstract

Mechanical forces are essential to the development and progression of fibrosis, and are likely to be as important as soluble factors. These forces regulate the phenotype and proliferation of myofibroblasts and other cells in damaged tissues, the activation of growth factors, the structure and mechanics of the matrix, and, potentially, tissue patterning. Better understanding of the variety and magnitude of forces, the characteristics of those forces in biological tissues, and their impact on fibrosis in multiple tissues is needed and may lead to identification of important new therapeutic targets. This article is part of a Special Issue entitled: Fibrosis: Translation of basic research to human disease.

Figure 1

Forces affecting tissues. A) Forces acting on tissues. B) The elastic modulus of a material is slope of the stress (force per unit area) plotted against the strain (deformation). The diagram demonstrates linear elasticity, where the stress/strain relationship is constant. In reality, most biological materials demonstrate non-linear elasticity, such that the elastic modulus changes as strain increases.

Figure 2

The role of mechanics in TGF-β activation. TGF-β is released in latent form, enclosed within the latency-associated peptide (LAP) as part of the TGF-β latent complex. Cell surface integrins, which connect to cytoplasmic actins at the site of focal adhesions, bind to LAP. As shown by Hinz and colleagues [36, 37], on soft surfaces (left) there is minimal resistance to cell generated tension and the complex remains latent. On stiff surfaces (right), there is significant resistance to cell-generated tension, this tension increases, and the LAP is pulled open, releasing active TGF-β.