Normal and Fibrotic Rat Livers Demonstrate Shear Strain Softening and Compression Stiffening: A Model for Soft Tissue Mechanics

• Published in: PLOS ONE Vol. 11; no. 1; p. e0146588
• Main Authors: Perepelyuk, Maryna, Chin, LiKang, Cao, Xuan, van Oosten, Anne, Shenoy, Vivek B., Janmey, Paul A., Wells, Rebecca G.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science (PLoS) 06.01.2016; Public Library of Science
• Subjects: Animal models; Animals; Bioengineering; Care and treatment; Collagen; Complications and side effects; Compressibility; Compression; Compressive Strength; Development and progression; Engineering schools; Extracellular matrix; Fibrosis; Glycosaminoglycans; Glycosaminoglycans - analysis; Growth factors; In Vitro Techniques; Incompressibility; Legal medicine; Liver; Liver - physiology; Liver Cirrhosis, Experimental; Liver Cirrhosis, Experimental - chemically induced; Liver Cirrhosis, Experimental - physiopathology; Liver diseases; Loss modulus; Materials science; Mathematical analysis; Matrix methods; Mechanical analysis; Mechanical properties; Mechanics; Mechanics (physics); Medicine; Models, Biological; Modulus of elasticity; Patient outcomes; Physiology; Plastic deformation; Q; R; Rats; Rats, Sprague-Dawley; Research Article; Rheometry; Rodents; Science; Shear modulus; Shear strain; Shear Strength; Softening; Stiffening; Stiffness; Strain; Stress (physiology); Stress, Mechanical; Tissues; Viscoelasticity; Water flow; United States
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0146588

Tissues including liver stiffen and acquire more extracellular matrix with fibrosis. The relationship between matrix content and stiffness, however, is non-linear, and stiffness is only one component of tissue mechanics. The mechanical response of tissues such as liver to physiological stresses is not well described, and models of tissue mechanics are limited. To better understand the mechanics of the normal and fibrotic rat liver, we carried out a series of studies using parallel plate rheometry, measuring the response to compressive, extensional, and shear strains. We found that the shear storage and loss moduli G' and G" and the apparent Young's moduli measured by uniaxial strain orthogonal to the shear direction increased markedly with both progressive fibrosis and increasing compression, that livers shear strain softened, and that significant increases in shear modulus with compressional stress occurred within a range consistent with increased sinusoidal pressures in liver disease. Proteoglycan content and integrin-matrix interactions were significant determinants of liver mechanics, particularly in compression. We propose a new non-linear constitutive model of the liver. A key feature of this model is that, while it assumes overall liver incompressibility, it takes into account water flow and solid phase compressibility. In sum, we report a detailed study of non-linear liver mechanics under physiological strains in the normal state, early fibrosis, and late fibrosis. We propose a constitutive model that captures compression stiffening, tension softening, and shear softening, and can be understood in terms of the cellular and matrix components of the liver.