Biomedical subjects

Stephen C Cowin

Publications and source records attributed to Stephen C Cowin.

12 recordsLinked to original sources

PubMed2005

Analysis of avian bone response to mechanical loading. Part two: Development of a computational connected cellular network to study bone intercellular communication.

Mechanical loading-induced signals are hypothesized to be transmitted and integrated by connected bone cells before reaching the bone surfaces where adaptation occurs. A computational connected cellular network (CCCN) model is developed to explore how bone cells perceive and transmit the signals through intercellular communication. This is part two of a two-part study in which a CCCN is developed to study the intercellular communication within a grid of bone cells. The excitation signal was computed as the loading-induced bone fluid shear stress in part one. Experimentally determined bone adaptation responses (Gross et al. in J Bone Miner Res 12:982-988, 1997 and Judex et al. in J Bone Miner Res 12:1737-1745, 1997) are correlated with the fluid shear stress by the CCCN, which adjusts cell sensitivities (loading and signal thresholds) and connection weights. Intercellular communication patterns extracted by the CCCN indicate the cell population responsible for perceiving the loading-induced signal, and loading threshold is shown to play an important role in regulating the bone response.

Algorithms↗

PubMed2005

Analysis of avian bone response to mechanical loading-Part one: Distribution of bone fluid shear stress induced by bending and axial loading.

Mechanical loading-induced signals are hypothesized to be transmitted and integrated by a bone-connected cellular network (CCN) before reaching the bone surfaces where adaptation occurs. Our objective is to establish a computational model to explore how bone cells transmit the signals through intercellular communication. In this first part of the study the bone fluid shear stress acting on every bone cell in a CCN is acquired as the excitation signal for the computational model. Bending and axial loading-induced fluid shear stress is computed in transverse sections of avian long bones for two adaptation experiments (Gross et al. in J Bone Miner Res 12:982-988, 1997 and Judex et al. in J Bone Miner Res 12:1737-1745, 1997). The computed fluid shear stress is found to be correlated with the radial strain gradient but not with bone formation. These results suggest that the radial strain gradient is the driving force for bone fluid flow in the radially distributed lacunar-canalicular system and that bone formation is not linearly related to the loading-induced local stimulus.

Animals↗

PubMed2005

Estimation of bone permeability using accurate microstructural measurements.

While interstitial fluid flow is necessary for the viability of osteocytes, it is also believed to play a role in bone's mechanosensory system by shearing bone cell membranes or causing cytoskeleton deformation and thus activating biochemical responses that lead to the process of bone adaptation. However, the fluid flow properties that regulate bone's adaptive response are poorly understood. In this paper, we present an analytical approach to determine the degree of anisotropy of the permeability of the lacunar-canalicular porosity in bone. First, we estimate the total number of canaliculi emanating from each osteocyte lacuna based on published measurements from parallel-fibered shaft bones of several species (chick, rabbit, bovine, horse, dog, and human). Next, we determine the local three-dimensional permeability of the lacunar-canalicular porosity for these species using recent microstructural measurements and adapting a previously developed model. Results demonstrated that the number of canaliculi per osteocyte lacuna ranged from 41 for human to 115 for horse. Permeability coefficients were found to be different in three local principal directions, indicating local orthotropic symmetry of bone permeability in parallel-fibered cortical bone for all species examined. For the range of parameters investigated, the local lacunar-canalicular permeability varied more than three orders of magnitude, with the osteocyte lacunar shape and size along with the 3-D canalicular distribution determining the degree of anisotropy of the local permeability. This two-step theoretical approach to determine the degree of anisotropy of the permeability of the lacunar-canalicular porosity will be useful for accurate quantification of interstitial fluid movement in bone.

Animals↗

PubMed2005

Tensile and compressive stress yield criteria for cancellous bone.

Experimentally based isotropic tensile and compressive strain yield criteria for cancellous bone are shown to imply tensile and compressive stress yield criteria, respectively. In particular, it is deduced that the directional variation of uniaxial yield stress is proportional to the one of Young's modulus. The obtained tensile and compressive stress yield criteria, in turn, imply information about the total stress yield criterion for cancellous bone.

Bone and Bones↗

PubMed2005

Dynamic shear stress in parallel-plate flow chambers.

An in vitro model using a parallel-plate fluid flow chamber is supposed to simulate in vivo fluid shear stresses on various cell types exposed to dynamic fluid flow in their physiological environment. The metabolic response of cells in vitro is associated with the wall shear stress. However, parallel-plate flow chambers have not been characterized for dynamic fluid flow experiments. We use a dimensionless ratio h / lambda(v), in determining the exact magnitude of the dynamic wall shear stress, with its oscillating components scaled by a shear factor T. It is shown that, in order to expose cells to predictable levels of dynamic fluid shear stress, two conditions have to be met: (1) h / lambda(v) < 2, where h is the distance between the plates and lambda(v) is the viscous penetration depth; and (2) f(0) < f(c) / m, where the critical frequency f(c) is the upper threshold for this flow regime, m is the highest harmonic mode of the flow, and f(0) is the fundamental frequency of fluid flow.

Animals↗

PubMed2004

Mechanotransduction and strain amplification in osteocyte cell processes.

A paradox in bone tissue is that tissue-level strains due to animal and human locomotion are too small to initiate intracellular chemical responses directly. A model recently was proposed to resolve this paradox, which predicts that the fluid flow through the pericellular matrix in the lacunar-canalicular porosity due to mechanical loading can induce strains in the actin filament bundles of the cytoskeleton that are more than an order of magnitude larger than tissue level strains. In this study, we greatly refine this model by using the latest ultrastructural data for the cell process cytoskeleton, the tethering elements that attach the process to the canalicular wall and their finite flexural rigidity EI. We construct a much more realistic 3D model for the osteocyte process and then use large-deformation "elastica" theory for finite EI to predict the deformed shape of the tethering elements and the hoop strain on the central actin bundle. Our model predicts a cell process that is 3 times stiffer than in a previous study but hoop strain of >0.5% for tissue-level strains of >1,000 microstrain at 1 Hz and >250 microstrain at frequencies >10 Hz. We propose that this strain-amplification model provides a more likely hypothesis for the excitation of osteocytes than the previously proposed fluid-shear hypothesis.

Actins↗

PubMed2004

Ultrastructure of the osteocyte process and its pericellular matrix.

Osteocytes are believed to be the mechanical sensor cells in bone. One potential physical mechanism for the mechanosensing process is that osteocytes directly sense the deformation of the substrate to which they are attached. However, there is a fundamental paradox in this theory: tissue-level strains in whole bone are typically <0.2%, yet an extensive range of in vitro experiments show that dynamic substrate strains must be at least an order of magnitude larger in order for intracellular biochemical responses to occur. Recently, a theoretical model was developed (You et al. J. Biomech., 2001; 34:1375-1386) that provides a possible mechanism by which mechanical loading-induced fluid flow in the lacuno-canalicular system, under routine physical activity, can produce cellular-level strains on the osteocyte processes that are at least one order of magnitude larger than bone tissue deformations. This would resolve the fundamental paradox mentioned above. In this work we experimentally confirm and quantify the essential ultrastructural elements in this model: 1) the presence of the transverse elements that bridge the pericellular space surrounding the osteocyte process, which interact with the fluid flow and lead to an outward hoop tension on the process; and 2) the presence of bundled F-actin in the osteocyte processes, which resists the outward hoop tension and limits the cell process membrane deformation. Morphological data to support these assumptions are scant. Special staining techniques employing ruthenium III hexamine trichloride (RHT) were developed to elucidate these structures in the humeri of adult mice.

Actins↗

PubMed2004

Tissue growth and remodeling.

The growth and remodeling of a tissue depends on certain features in the history of its mechanical environment as well as its genetic makeup. The mechanical environment influences the tissue's developing morphology, the process of simply increasing the size of existing morphological structures, and the formation of the proteins of which the tissue is constructed. The relationships between genetic information, various epigenetic mechanisms and tissue development are discussed. The developmental growth and remodeling of most structural tissues are enhanced by the use of those tissues and retarded by their disuse. The mechanical or mathematical modeling of tissue growth and development using cellular automata models and continuum mechanical models is reviewed.

Animals↗

PubMed2003

Mechanotransduction and flow across the endothelial glycocalyx.

In this inaugural paper, we shall provide an overview of the endothelial surface layer or glycocalyx in several roles: as a transport barrier, as a porous hydrodynamic interface in the motion of red and white cells in microvessels, and as a mechanotransducer of fluid shearing stresses to the actin cortical cytoskeleton of the endothelial cell. These functions will be examined from a new perspective, the quasiperiodic ultrastructural model proposed in Squire et al. [Squire, J. M., Chew, M., Nneji, G., Neal, C., Barry, J. & Michel, C. (2001) J. Struct. Biol. 136, 239-255] for the 3D organization of the endothelial surface layer and its linkage to the submembranous scaffold. We shall show that the core proteins in the bush-like structures comprising the matrix have a flexural rigidity, EI, that is sufficiently stiff to serve as a molecular filter for plasma proteins and as an exquisitely designed transducer of fluid shearing stresses. However, EI is inadequate to prevent the buckling of these protein structures during the intermittent motion of red cells or the penetration of white cell microvilli. In these cellular interactions, the viscous draining resistance of the matrix is essential for preventing adhesive molecular interactions between proteins in the endothelial membrane and circulating cellular components.

Actins↗

PubMed2003

On bone adaptation due to venous stasis.

This paper addresses the question of whether or not interstitial fluid flow due to the blood circulation accounts for the observed periosteal bone formation associated with comprised venous return (venous stasis). Increased interstitial fluid flow induced by increased intramedullary pressure has been proposed to account for the periosteal response in venous stasis. To investigate the shear stresses acting on bone cell processes due to the blood circulation-driven interstitial fluid flow, a poroelastic model is extended to the situation in which the interstitial fluid flow in an osteon is driven by the pulsatile extravascular pressure in the osteonal canal as well as by the applied cyclic mechanical loading. Our results show that under normal conditions, the pulsatile extravascular pressure in the osteonal canal due to cardiac contraction (10mm Hg at 2Hz) and skeletal muscle contraction (30mm Hg at 1Hz) induce peak shear stresses on the osteocyte cell processes that are two orders of magnitude lower than those induced by physiological mechanical loading (100 microstrain at 1Hz). In venous stasis the induced peak shear stress is reduced further compared to the normal conditions because, although the mean intramedullary pressure is increased, the amplitude of its pulsatile component is decreased. These results suggest that the interstitial fluid flow is unlikely to cause the periosteal bone formation in venous stasis. However, the mean interstitial fluid pressure is found to increase in venous stasis, which may pressurize the periosteum and thus play a role in periosteal bone formation.

Adaptation, Physiological↗

PubMed2002

Fluid shear stress remodels expression and function of junctional proteins in cultured bone cells.

We tested the hypothesis that fluid shear stress (tau) modifies the expression, function, and distribution of junctional proteins [connexin (Cx)43, Cx45, and zona occludens (ZO)-1] in cultured bone cells. Cell lines with osteoblastic (MC3T3-E1 cells) and osteocytic (MLO-Y4 cells) phenotypes were exposed to tau-values of 5 or 20 dyn/cm(2) for 1-3 h. Immunostaining indicated that at 5 dyn/cm(2), the distribution of Cx43, Cx45, and ZO-1 was moderately disrupted at cell membranes; at 20 dyn/cm(2), disruption was more severe. Intercellular coupling was significantly decreased at both shear stress levels. Western blots showed the downregulation of membrane-bound Cx43 and ZO-1 and the upregulation of cytosolic Cx43 and Cx45 at different levels of shear stress. Similarly, Northern blots revealed that expression of Cx43, Cx45, and ZO-1 was selectively up- and downregulated in response to different shear stress levels. These results indicate that in cultured bone cells, fluid shear stress disrupts junctional communication, rearranges junctional proteins, and determines de novo synthesis of specific connexins to an extent that depends on the magnitude of the shear stress. Such disconnection from the bone cell network may provide part of the signal whereby the disconnected cells or the remaining network initiate focal bone remodeling.

Alkaline Phosphatase↗

PubMed2002

Estimation of the poroelastic parameters of cortical bone.

Cortical bone has two systems of interconnected channels. The largest of these is the vascular porosity consisting of Haversian and Volkmann's canals, with a diameter of about 50 microm, which contains a.o. blood vessels and nerves. The smaller is the system consisting of the canaliculi and lacunae: the canaliculi are at the submicron level and house the protrusions of the osteocytes. When bone is differentially loaded, fluids within the solid matrix sustain a pressure gradient that drives a flow. It is generally assumed that the flow of extracellular fluid around osteocytes plays an important role not only in the nutrition of these cells, but also in the bone's mechanosensory system. The interaction between the deformation of the bone matrix and the flow of fluid can be modelled using Biot's theory of poroelasticity. However, due to the inhomogeneity of the bone matrix and the scale of the porosities, it is not possible to experimentally determine all the parameters that are needed for numerical implementation. The purpose of this paper is to derive these parameters using composite modelling and experimental data from literature. A full set of constants is estimated for a linear isotropic description of cortical bone as a two-level porous medium. Bone, however, has a wide variety of mechanical and structural properties; with the theoretical relationships described in this note, poroelastic parameters can be derived for other bone types using their specific experimental data sets.

Bone Matrix↗