title: A model for strain amplification in the actin cytoskeleton of osteocytes due to fluid drag on pericellular matrix.
abstract: A model is presented that provides a resolution to a fundamental paradox in bone physiology, namely, that the strains applied to whole bone (i.e., tissue level strains) are much smaller (0.04-0.3 percent) than the strains (1-10 percent) that are necessary to cause bone signaling in deformed cell cultures (Rubin and Lanyon, J. Bone Joint Surg. 66A (1984) 397-410; Fritton et al., J. Biomech. 33 (2000) 317-325). The effect of fluid drag forces on the pericellular matrix (PM), its coupling to the intracellular actin cytoskeleton (IAC) and the strain amplification that results from this coupling are examined for the first time. The model leads to two predictions, which could fundamentally change existing views. First, for the loading range 1-20MPa and frequency range 1-20Hz, it is, indeed, possible to produce cellular level strains in bone that are up to 100 fold greater than normal tissue level strains (0.04-0.3 percent). Thus, the strain in the cell process membrane due to the loading can be of the same order as the in vitro strains measured in cell culture studies where intracellular biochemical responses are observed for cells on stretched elastic substrates. Second, it demonstrates that in any cellular system, where cells are subject to fluid flow and tethered to more rigid supporting structures, the tensile forces on the cell due to the drag forces on the tethering fibers may be many times greater than the fluid shear force on the cell membrane.
authors.affiliation: Department of Mechanical Engineering, The Center for Biomedical Engineering, City College of New York, The City University of New York, Convent Avenue at 140th Street, New York, NY 10031, USA.
authors.forename: L
authors.initials: L
authors.lastname: You
authors.forename: S C
authors.initials: SC
authors.lastname: Cowin
authors.forename: M B
authors.initials: MB
authors.lastname: Schaffler
authors.forename: S
authors.initials: S
authors.lastname: Weinbaum
mesh_terms: D000199:Actins / Q000502:physiology*; D000818:Animals; D001826:Body Fluids; D001857:Bone Matrix / Q000502:physiology; D001842:Bone and Bones / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology; D003599:Cytoskeleton / Q000502:physiology*; D005109:Extracellular Matrix / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D010011:Osteocytes / Q000502:physiology* / Q000648:ultrastructure; D012212:Rheology; D013314:Stress, Mechanical; D013718:Tensile Strength; D016474:Weight-Bearing
chemical_list: D000199:Actins