title: Normal and Fibrotic Rat Livers Demonstrate Shear Strain Softening and Compression Stiffening: A Model for Soft Tissue Mechanics.
abstract: 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.
authors.affiliation: Department of Medicine, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Maryna
authors.initials: M
authors.lastname: Perepelyuk
authors.affiliation: The Institute for Medicine and Engineering, The University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.|Department of Physiology, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.|Clinical Research Center for Diabetes, Tokushima University Hospital, Tokushima, Japan.
authors.forename: LiKang
authors.initials: L
authors.lastname: Chin
authors.affiliation: Department of Materials Science and Engineering, School of Engineering and Applied Sciences, The University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Xuan
authors.initials: X
authors.lastname: Cao
authors.affiliation: The Institute for Medicine and Engineering, The University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.|Department of Bioengineering, School of Engineering and Applied Sciences, The University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Anne
authors.initials: A
authors.lastname: van Oosten
authors.affiliation: Department of Materials Science and Engineering, School of Engineering and Applied Sciences, The University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Vivek B
authors.initials: VB
authors.lastname: Shenoy
authors.affiliation: The Institute for Medicine and Engineering, The University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.|Department of Physiology, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Janmey
authors.affiliation: Department of Medicine, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Rebecca G
authors.initials: RG
authors.lastname: Wells
mesh_terms: D000818:Animals; D019245:Compressive Strength; D006025:Glycosaminoglycans / Q000032:analysis; D066298:In Vitro Techniques; D008099:Liver / Q000502:physiology*; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000503:physiopathology; D008954:Models, Biological; D051381:Rats; D017207:Rats, Sprague-Dawley; D033081:Shear Strength; D013314:Stress, Mechanical
chemical_list: D006025:Glycosaminoglycans