scholarly journals Continuum Modeling of Biological Tissue Growth by Cell Division, and Alteration of Intracellular Osmolytes and Extracellular Fixed Charge Density

2009 ◽  
Vol 131 (10) ◽  
Author(s):  
Gerard A. Ateshian ◽  
Kevin D. Costa ◽  
Evren U. Azeloglu ◽  
Barclay Morrison ◽  
Clark T. Hung

A framework is formulated within the theory of mixtures for continuum modeling of biological tissue growth that explicitly addresses cell division, using a homogenized representation of cells and their extracellular matrix (ECM). The model relies on the description of the cell as containing a solution of water and osmolytes, and having a porous solid matrix. The division of a cell into two nearly identical daughter cells is modeled as the doubling of the cell solid matrix and osmolyte content, producing an increase in water uptake via osmotic effects. This framework is also generalized to account for the growth of ECM-bound molecular species that impart a fixed charge density (FCD) to the tissue, such as proteoglycans. This FCD similarly induces osmotic effects, resulting in extracellular water uptake and osmotic pressurization of the ECM interstitial fluid, with concomitant swelling of its solid matrix. Applications of this growth model are illustrated in several examples.

Author(s):  
Gerard A. Ateshian ◽  
Kevin D. Costa ◽  
Evren U. Azeloglu ◽  
Barclay Morrison ◽  
Clark T. Hung

A framework is formulated for continuum modeling of biological tissue growth that explicitly addresses cell division, using a homogenized representation of cells and the extracellular matrix (ECM). The essential elements of this model rely on the description of the cell as containing a solution of water and osmolytes, and having osmotically inactive solid constituents that may be generically described as a porous solid matrix. The division of a cell into two nearly identical daughter cells normally starts with the duplication of cell contents during the synthesis phase, followed by cell division during the mitosis phase. Thus, ultimately, cell division is equivalent to doubling of the cell solid matrix and osmolyte content, and a resulting increase in water uptake via osmotic effects. In a homogenized representation of the tissue, the geometry of individual cells is not modeled explicitly, but their solid matrix and intracellular osmolyte content can be suitably incorporated into the analysis of the tissue response, thereby accounting for their osmotic effects. Thus, cell division can be described by the growth of these cell constituents, including the accumulation of osmotically active content, and the resultant uptake of water.


1991 ◽  
Vol 113 (3) ◽  
pp. 245-258 ◽  
Author(s):  
W. M. Lai ◽  
J. S. Hou ◽  
V. C. Mow

Swelling of articular cartilage depends on its fixed charge density and distribution, the stiffness of its collagen-proteoglycan matrix, and the ion concentrations in the interstitium. A theory for a tertiary mixture has been developed, including the two fluid-solid phases (biphasic), and an ion phase, representing cation and anion of a single salt, to describe the deformation and stress fields for cartilage under chemical and/or mechanical loads. This triphasic theory combines the physico-chemical theory for ionic and polyionic (proteoglycan) solutions with the biphasic theory for cartilage. The present model assumes the fixed charge groups to remain unchanged, and that the counter-ions are the cations of a single salt of the bathing solution. The momentum equation for the neutral salt and for the intersitial water are expressed in terms of their chemical potentials whose gradients are the driving forces for their movements. These chemical potentials depend on fluid pressure p, salt concentration c, solid matrix dilatation e and fixed charge density cF. For a uni-uni valent salt such as NaCl, they are given by μi = μoi + (RT/Mi)ln[γ±2c (c + c F)] and μW = μow + [p − RTφ(2c + cF) + Bwe]/ρTw, where R, T, Mi, γ±, φ, ρTw and Bw are universal gas constant, absolute temperature, molecular weight, mean activity coefficient of salt, osmotic coefficient, true density of water, and a coupling material coefficient, respectively. For infinitesimal strains and material isotropy, the stress-strain relationship for the total mixture stress is σ = − pI − TcI + λs(trE)I + 2μsE, where E is the strain tensor and (λs,μs) are the Lame´ constants of the elastic solid matrix. The chemical-expansion stress (− Tc) derives from the charge-to-charge repulsive forces within the solid matrix. This theory can be applied to both equilibrium and non-equilibrium problems. For equilibrium free swelling problems, the theory yields the well known Donnan equilibrium ion distribution and osmotic pressure equations, along with an analytical expression for the “pre-stress” in the solid matrix. For the confined-compression swelling problem, it predicts that the applied compressive stress is shared by three load support mechanisms: 1) the Donnan osmotic pressure; 2) the chemical-expansion stress; and 3) the solid matrix elastic stress. Numerical calculations have been made, based on a set of equilibrium free-swelling and confined-compression data, to assess the relative contribution of each mechanism to load support. Our results show that all three mechanisms are important in determining the overall compressive stiffness of cartilage.


2008 ◽  
Vol 294 (3) ◽  
pp. H1197-H1205 ◽  
Author(s):  
Evren U. Azeloglu ◽  
Michael B. Albro ◽  
Vikrum A. Thimmappa ◽  
Gerard A. Ateshian ◽  
Kevin D. Costa

The arterial wall contains a significant amount of charged proteoglycans, which are inhomogeneously distributed, with the greatest concentrations in the intimal and medial layers. The hypothesis of this study is that the transmural distribution of proteoglycans plays a significant role in regulating residual stresses in the arterial wall. This hypothesis was first tested theoretically, using the framework of mixture theory for charged hydrated tissues, and then verified experimentally by measuring the opening angle of rat aorta in NaCl solutions of various ionic strengths. A three-dimensional finite element model of aortic ring, using realistic values of the solid matrix shear modulus and proteoglycan fixed-charge density, yielded opening angles and changes with osmolarity comparable to values reported in the literature. Experimentally, the mean opening angle in isotonic saline (300 mosM) was 15 ± 17° and changed to 4 ± 19° and 73 ± 18° under hypertonic (2,000 mosM) and hypotonic (0 mosM) conditions, respectively ( n = 16). In addition, the opening angle in isotonic (300 mosM) sucrose, an uncharged molecule, was 60 ± 16° ( n = 11), suggesting that the charge effect, not cellular swelling, was the major underlying mechanism for these observations. The extent of changes in opening angle under osmotic challenges suggests that transmural heterogeneity of fixed-charge density plays a crucial role in governing the zero-stress configuration of the aorta. A significant implication of this finding is that arterial wall remodeling in response to altered wall stresses may occur via altered deposition of proteoglycans across the wall thickness, providing a novel mechanism for regulating mechanical homeostasis in vascular tissue.


2003 ◽  
Vol 125 (1) ◽  
pp. 12-24 ◽  
Author(s):  
James C. Iatridis ◽  
Jeffrey P. Laible ◽  
Martin H. Krag

A 3-dimensional formulation for a poroelastic and chemical electric (PEACE) model is presented and applied to an intervertebral disc slice in a 1-dimensional validation problem and a 2-dimensional plane stress problem. The model was used to investigate the influence of fixed charge density magnitude and distribution on this slice of disc material. Results indicated that the mechanical, chemical, and electrical behaviors were all strongly influenced by the amount as well as the distribution of fixed charges in the matrix. Without any other changes in material properties, alterations in the fixed charge density (proteoglycan content) from a healthy to a degenerated distribution will cause an increase in solid matrix stresses and can affect whether the tissue imbibes or exudes fluid under different loading conditions. Disc tissue with a degenerated fixed charge density distribution exhibited greater solid matrix stresses and decreased streaming potential, all of which have implications for disc nutrition, disc biomechanics, and tissue remodeling. It was also seen that application of an electrical potential across the disc can induce fluid transport.


2000 ◽  
Author(s):  
W. M. Lai ◽  
D. D. Sun ◽  
G. A. Ateshian ◽  
X. E. Guo ◽  
V. C. Mow

Abstract An important step toward understanding the signal transduction mechanisms that modulate cellular activities is the accurate prediction of the mechanical and electro-chemical environment of the cells in well-defined experimental configurations. One such configuration is the steady permeation experiment (e.g., bioreactors) in the open circuit condition. Using our triphasic theory, we have calculated the strain, velocity and the electric potential fields inside a layer of charged articular cartilage, through which a uni-univalent salt (e.g., NaCl) solution permeates under a constant pressure difference across the layer. The fluid flow through the tissue gives rise to an electrical potential difference across the tissue. This potential difference is the well-known “streaming potential” that is measured by Ag/AgCl electrodes placed across the tissue on the outside. Our results show that inside the tissue, in addition to the streaming potential caused by fluid convection, there is also a “diffusion potential” caused by cation and anion concentration gradients that are induced by the gradient of fixed charge density (FCD) inside the tissue. The gradient of FCD may be intrinsic, i.e., the tissue has an inhomogeneous FCD distribution, or it may also be caused by a non-uniform compaction of the solid matrix as is the case in steady permeation where the drag force exerted by the permeating fluid onto the solid matrix causes a compressive strain field inside the tissue. In this experimental configuration, the diffusion potential would compete against the streaming potential. The magnitude and the polarity of the electric field depend, amongst other material parameters, on the compressive stiffness of the tissue. For softer tissue (e.g., aggregate modulus <0.54 MPa for a set of realistic material and testing parameters), the diffusion potential dominates over the streaming potential and vice versa for stiffer tissue. For articular cartilage what the cells see in situ is the combined electrical effect of intrinsic and deformation induced inhomogeneity of FCD. The present results provide not only quantitative information, but also new insight into an important problem in biotechnology. These results also demonstrate that for proper interpretation of the mechano-electrochemical signal transduction mechanisms that is needed for modulating cellular biosynthetic activities, one must not ignore the important effects of diffusion potential.


2002 ◽  
Vol 47 (2) ◽  
pp. 284-291 ◽  
Author(s):  
Erik M. Shapiro ◽  
Arijitt Borthakur ◽  
Alexander Gougoutas ◽  
Ravinder Reddy

2002 ◽  
pp. 387-395
Author(s):  
Robert J. Wilkins ◽  
Bethan Hopewell ◽  
Jill P. G. Urban

1988 ◽  
Vol 254 (3) ◽  
pp. F364-F373 ◽  
Author(s):  
M. Wolgast ◽  
G. Ojteg

In the classical Starling model the hydrostatic pressure in the pores is generally lower than that in capillary plasma, a phenomenon that necessitates the assumption of a rigid porous membrane. In flexible gel membranes, the capillary pressure is suggested to be balanced by a gel swelling pressure generated by negative fixed charges. Regarding the fluid transfer, the transmembranous electrical potential gradient will generate a net driving electroosmotic force. This force will be numerically similar to the net driving Starling force in small pores, but distinctly different in large pores. From previous data on the hydrostatic and colloid osmotic forces, the fixed charge density at the two interfaces of 1) the glomerular and 2) the peritubular capillary membrane were calculated and used to predict the flux of a series of charged protein probes. The close fit to the experimental data in both the capillary beds is in line with the gel concept presented. The gel concept (but hardly a rigid membrane) explains the ability of capillary membranes to alter their permeability in response to external forces. Gel membranes can furthermore be predicted to have a self-rinsing ability, as entrapped proteins will increase the local fixed charge density, leading to fluid entry into the region between the particle and the pore rim, which by consequent widening of the channel will facilitate extrusion of trapped proteins.


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