A distributed nonlinear model of lung tissue elasticity

Maksym, Geoffrey N., and Jason H. T. Bates. Adistributed nonlinear model of lung tissue elasticity.J. Appl. Physiol. 82(1): 32-41, 1997.- We present a theory relating the static stress-strainproperties of lung tissue strips to the stress-bearing constituents,collagen and elastin. The fiber pair is modeled as a Hookean spring(elastin) in parallel with a nonlinear string element (collagen), whichextends to a maximum stop length. Based on a series of fiber pairs, wedevelop both analytical and numerical models with distributedconstituent properties that account for nonlinear tissue elasticity.The models were fit to measured stretched stress-strain curves of fiveuniaxially stretched tissue strips, each from a different dog lung. Wefound that the distributions of stop length and spring stiffness followinverse power laws, and we hypothesize that this results from thecomplex fractal-like structure of the constituent fiber matrices inlung tissue. We applied the models to representative pressure-volume(PV) curves from patients with normal, emphysematous,and fibrotic lungs. The PV curves were fit to theequation V = A  Bexp(KP),where V is volume, P is transpulmonary pressure, andA, B, andK are constants. Our models lead to apossible mechanistic explanation of the shape factorK in terms of the structuralorganization of collagen and elastin fibers.

     

A viscoelastic two-dimensional network model of the lung extracellular matrix

Biomechanics and Modeling in Mechanobiology - The extracellular matrix (ECM) comprises a large proportion of the lung parenchymal tissue and is an important contributor to the mechanical properties...     

A cellular model of lung elasticity

The mechanics of the lung parenchyma is studied using models comprised of line members interconnected to form 3-D cellular structures. The mechanical properties are represented as elastic constants of a continuum. These are determined by perturbing each individual cell from a reference state by an increment in stress which is superimposed upon the uniform stretching forces initially present in the members due to the transpulmonary pressure. A force balance on the distorted structure, together with a force-deformation law for the members, leads to a calculation of the strain increments of the members. Predictions based on the analysis of the 3-D isotropic dodecahedron are in good agreement with experimental values for the Young's, shear, and bulk moduli reported in the literature. The model provides an explanation for the dependence of the elastic moduli on transpulmonary pressure, the geometrical details of the structure, and the stress-strain law of the tissue.     

Surface tension and the dodecahedron model for lung elasticity

Macroscopic elastic moduli governing the incremental deformations of lung parenchyma are calculated on the basis of a model for an individual lung element in the shape of a regular dodecahedron. Elastic stiffness within the element is provided by pin-jointed tension members along the edges of the dodecahedron, surface tension is incorporated into its pentagonal faces, and the influence of transpulmonary pressure is simulated by an externally applied hydrostatic tension. The analysis is based on a variational statement of nonlinear structural mechanics, and the results show how the moduli depend on the effective inflation pressure, the constitutive behavior of the idealized truss members, and the surface-area dependent surface tension. The theory is discussed in the light of available experimental information. A more general analysis is needed to account for the effects of structural as well as surface-tension hysteresis.     

Spatial and temporal heterogeneity explain disease dynamics in a spatially explicit network model

There is an increasing recognition that individual-level spatial and temporal heterogeneity may play an important role in metapopulation dynamics and persistence. In particular, the patterns of contact within and between aggregates (e.g., demes) at different spatial and temporal scales may reveal important mechanisms governing metapopulation dynamics. Using 7 years of data on the interaction between the anther smut fungus (Microbotryum violaceum) and fire pink (Silene virginica), we show how the application of spatially explicit and implicit network models can be used to make accurate predictions of infection dynamics in spatially structured populations. Explicit consideration of both spatial and temporal organization reveals the role of each in spreading risk for both the host and the pathogen. This work suggests that the application of spatially explicit network models can yield important insights into how heterogeneous structure can promote the persistence of species in natural landscapes.     

Genetically determined heterogeneity of lung disease in a mouse model of airway mucus obstruction

Mucus clearance is an important airway innate defense mechanism. Airway-targeted overexpression of the epithelial Na(+) channel β-subunit [encoded by sodium channel nonvoltage gated 1, beta subunit (Scnn1b)] in mice [Scnn1b-transgenic (Tg) mice] increases transepithelial Na(+) absorption and dehydrates the airway surface, which produces key features of human obstructive lung diseases, including mucus obstruction, inflammation, and air-space enlargement. Because the first Scnn1b-Tg mice were generated on a mixed background, the impact of genetic background on disease phenotype in Scnn1b-Tg mice is unknown. To explore this issue, congenic Scnn1b-Tg mice strains were generated on C57BL/6N, C3H/HeN, BALB/cJ, and FVB/NJ backgrounds. All strains exhibited a two- to threefold increase in tracheal epithelial Na(+) absorption, and all developed airway mucus obstruction, inflammation, and air-space enlargement. However, there were striking differences in neonatal survival, ranging from 5 to 80% (FVB/NJ相似文献   

Effect of stochastic heterogeneity on lung impedance during acute bronchoconstriction: a model analysis

Thorpe, C. William, and Jason H. T. Bates. Effect ofstochastic heterogeneity on lung impedance during acutebronchoconstriction: a model analysis. J. Appl.Physiol. 82(5): 1616-1625, 1997.In a previousstudy (J. H. T. Bates, A. M. Lauzon, G. S. Dechman, G. N. Maksym, and T. F. Schuessler. J. Appl.Physiol. 76: 616-626, 1994), we investigated theacute changes in isovolume lung mechanics immediately after a bolusinjection of histamine. We found that dynamic resistance and elastanceincreased progressively in the 80-s period after injection, whereas theestimated tissue hysteresivity reached a stable plateau after ~25 s.In the present study, we developed a computer model of the lung toinvestigate the mechanisms responsible for these observations. Themodel conforms to Horsfield's morphometry, with the addition ofcompliant airways and structural damping tissue units. Using thismodel, we simulated the time course of acute bronchoconstriction afterintravenous administration of a bolus of bronchial agonist.Heterogeneity was induced by randomly varying the values of the maximalairway smooth muscle contraction and the tissue response to theagonist. Our results demonstrate that much of the increase in lungimpedance observed in our previous study can be produced purely by theeffects of airway heterogeneity. However, we were only able toreproduce the plateauing of hysteresivity by assigning a minimum radius to each airway, beyond which it would immediately snap completely shut.We propose that airway closure played an important role in ourexperimental observations.

     

Strain-induced reorientation of an intramuscular connective tissue network: implications for passive muscle elasticity

The most abundant intramuscular connective tissue component, the perimysium, of bovine M. sternomandibularis muscle was shown to be a crossed-ply arrangement of crimped collagen fibres which reorientate and decrimp on changing muscle fibre sarcomere length. Reorientation of perimysial strands was observed by light microscopy and identification of these strands as collagen fibres was confirmed by high-angle X-ray diffraction. Mean collagen fibre direction with respect to the muscle fibres ranged from approximately 80 degrees at sarcomere length = 1.1 micron to approximately 20 degrees at 3.9 microns. This behaviour was well described by a model of a crimped planar network surrounding a muscle fibre bundle of constant volume but varying length. Modelling of the mechanical properties of the perimysium at different sarcomere lengths produced a load-sarcomere length curve which was in good agreement with the passive elastic properties of the muscle, especially at long sarcomere lengths. It is concluded that the role of the perimysial collagen network is to prevent over-stretching of the muscle fibre bundles.     

Dendritic cell functional properties in a three-dimensional tissue model of human lung mucosa

In lung tissue, dendritic cells (DC) are found in close association with the epithelial cell layer, and there is evidence of DC regulation by the epithelium; that epithelial dysfunction leads to overzealous immune cell activation. However, dissecting basic mechanisms of DC interactions with epithelial cells in human tissue is difficult. Here, we describe a method to generate a three-dimensional organotypic model of the human airway mucosa in which we have implanted human DC. The model recapitulates key anatomical and functional features of lung mucosal tissue, including a stratified epithelial cell layer, deposition of extracellular matrix proteins, and the production of tight junction and adherence junction proteins. Labeling of fixed tissue model sections and imaging of live tissue models also revealed that DC distribute in close association with the epithelial layer. As functional properties of DC may be affected by the local tissue microenvironment, this system provides a tool to study human DC function associated with lung mucosal tissue. As an example, we report that the lung tissue model regulates the capacity of DC to produce the chemokines CCL17, CCL18, and CCL22, leading to enhanced CCL18 expression and reduced CCL17 and CCL22 expression. This novel tissue model thus provides a tool well suited for a wide range of studies, including those on the regulation of DC functional properties within the local tissue microenvironment during homeostasis and inflammatory reactions.     

A tissue-engineered model of fetal distal lung tissue

In extending our previous studies toward development of an engineered distal lung tissue construct (M. J. Mondrinos, S. Koutzaki, E. Jiwanmall, M. Li, J. P. Dechadarevian, P. I. Lelkes, and C. M. Finck. Tissue Eng 12: 717-728, 2006), we studied the effects of exogenous fibroblast growth factors FGF10, FGF7, and FGF2 on mixed populations of embryonic day 17.5 murine fetal pulmonary cells cultured in three-dimensional collagen gels. The morphogenic effects of the FGFs alone and in various combinations were assessed by whole mount immunohistochemistry and confocal microscopy. FGF10/7 significantly increased epithelial budding and proliferation; however, only FGF10 alone induced widespread budding. FGF7 alone induced dilation of epithelial structures but not widespread budding. FGF2 alone had a similar dilation, but not budding, effect in epithelial structures, and, in addition, significantly enhanced endothelial tubular morphogenesis and network formation, as well as mesenchymal proliferation. The combination of FGF10/7/2 induced robust budding of epithelial structures and the formation of uniform endothelial networks in parallel. These data suggest that appropriate combinations of exogenous FGFs chosen to target specific FGF receptor isoforms will allow for control of lung epithelial and mesenchymal cell behavior in the context of an engineered system. We propose that tissue-engineered fetal distal lung constructs could provide a potential source of tissue or cells for lung augmentation in pediatric pulmonary pathologies, such as pulmonary hypoplasia and bronchopulmonary dysplasia. In addition, engineered systems will provide alternative in vitro venues for the study of lung developmental biology and pathobiology.     

A tethered adhesive particle model of two-dimensional elasticity and its application to the erythrocyte membrane.

A new model of two-dimensional elasticity with application to the erythrocyte membrane is proposed. The system consists of a planar array of self-adhesive particles attached to nearest neighbors with flexible tethers. Stretching from the equilibrium dimension is resisted because force is required to dissociate the particle clusters and to decrease the distribution entropy. Release of the external force is accompanied by a contraction as thermal diffusion randomizes the particles and allows interparticle attachments to form again. Analysis of membrane thermodynamics and mechanics under the two-state particle assumption results in a shear softening stress-strain relation. The shear modulus is found proportional to the square root of the surface density of particles, the interparticle adhesive energy, and is inversely proportional to the tether length. Applied to the erythrocyte membrane under the assumption that band 3 tetramer represents the particle and spectrin the tether, the shear modulus predicted corresponds to the measured value when the interparticle adhesive energy is approximately 4.0-5.9 kT, where kT is the Boltzmann constant multiplied by the temperature. This model suggests a mechanism wherein erythrocyte membrane deformability depends on integral protein homomultimeric interactions and can be modulated from the external surface.     

Platelets induce endothelial tissue factor expression in a mouse model of acid-induced lung injury

Although the lung expresses procoagulant proteins under inflammatory conditions, underlying mechanisms remain unclear. Here, we addressed lung endothelial expression of tissue factor (TF), which initiates the coagulation cascade and expression of which signifies development of a procoagulant phenotype in the vasculature. To establish the model of acid-induced acute lung injury (ALI), we intranasally instilled anesthetized mice with saline or acid. Then 2 h later, we isolated pulmonary vascular cells for flow cytometry and confocal microscopy to detect the leukocyte antigen, CD45 and the endothelial markers VE-cadherin and von Willebrand factor (vWf). Acid increased both the number of vWf-expressing cells as well as TF and P-selectin expressions on these cells. All of these effects were markedly inhibited by treating mice with antiplatelet serum, suggesting the involvement of platelets. The increased expressions of TF, vWf, and P-selectin in response to acid also occurred in platelets. Moreover, the effects were replicated in endothelial cells derived from isolated, blood-perfused lungs. However, the effect was inhibited completely in lungs perfused with platelet-depleted and, to a lesser extent, with leukocyte-depleted blood. Acid injury increased endothelial expressions of the platelet proteins, CD41 and CD42b, providing evidence that platelet proteins were transferred to the vascular surface. Reactive oxygen species (ROS) were implicated in these responses, in that the endothelial and platelet protein expressions were inhibited. We conclude that acid-induced ALI causes NOX2-mediated ROS generation that activates platelets, which then generate a procoagulant endothelial surface.     

Seasonal changes in tissue elasticity in chaparral shrubs

An important physiological feature of chaparral shrubs is the development of low water potentials during periods of drought characteristic of southern Californian summers. Changes in tissue elasticity may be an important characteristic allowing these low water potentials to be reached and maintained without the development of detrimental water deficits. To examine this possibility, seasonal changes in tissue elasticity were measured in 3 species of chaparral shrubs, Arctostaphylos glandulosa Eastw., Quercus dumosa Nutt. and Ceanothus greggii Gray., by the pressure-volume method. Tissue elasticity was characterized using graphs of the modulus of elasticity plotted as a function of turgor pressure, and maximum values of the elastic modulus. The moduli of elasticity of the shrubs increased following leaf emergence in the spring, were highest during periods of low soil water potential, and tended to decrease following the summer-fall drought period. Increases in tissue elasticity facilitate water uptake from drying soils, but result in greater turgor loss during tissue dehydration.     

Force feasible set prediction with artificial neural network and musculoskeletal model

Abstract

Developing tools to predict the force capabilities of the human limbs through the Force Feasible Set (FFS) may be of great interest for robotic assisted rehabilitation and digital human modelling for ergonomics. Indeed, it could help to refine rehabilitation programs for active participation during exercise therapy and to prevent musculoskeletal disorders. In this framework, the purpose of this study is to use artificial neural networks (ANN) to predict the FFS of the upper-limb based on joint centre Cartesian positions and anthropometric data. Seventeen right upper-limb musculoskeletal models based on individual anthropometric data are created. For each musculoskeletal model, the FFS is computed for 8428 different postures. For any combination of force direction and joint positions, ANNs can predict the FFS with high values of coefficient of determination (R²?>?0.89) between the true and predicted data.     

A nonlinear viscoelastic model of lung tissue mechanics.

There have been a number of attempts recently to use linear models to describe the low-frequency (0-2 Hz) dependence of lung tissue resistance (Rti) and elastance (Eti). Only a few attempts, however, have been made to account for the volume dependence of these quantities, all of which require the tissues to be plastoelastic. In this paper we specifically avoid invoking plastoelasticity and develop a nonlinear viscoelastic model that is also capable of accounting for the nonlinear and frequency-dependent features of lung tissue mechanics. The model parameters were identified by fitting the model to data obtained in a previous study from dogs during sinusoidal ventilation. The model was then used to simulate pressure and flow data by use of various types of ventilation patterns similar to those that have been employed experimentally. Rti and Eti were estimated from the simulated data by use of four different estimation techniques commonly applied in respiratory mechanics studies. We found that the estimated volume dependence of Rti and Eti is sensitive to both the ventilation pattern and the estimation technique, being in error by as much as 217 and 22%, respectively.