The influence and biomechanical role of cartilage split line pattern on tibiofemoral cartilage stress distribution during the stance phase of gait

This study presents an evaluation of the role that cartilage fibre ‘split line’ orientation plays in informing femoral cartilage stress patterns. A two-stage model is presented consisting of a whole knee joint coupled to a tissue-level cartilage model for computational efficiency. The whole joint model may be easily customised to any MRI or CT geometry using free-form deformation. Three ‘split line’ patterns (medial–lateral, anterior–posterior and random) were implemented in a finite element model with constitutive properties referring to this ‘split line’ orientation as a finite element fibre field. The medial–lateral orientation was similar to anatomy and was derived from imaging studies. Model predictions showed that ‘split lines’ are formed along the line of maximum principal strains and may have a biomechanical role of protecting the cartilage by limiting the cartilage deformation to the area of higher cartilage thickness.     

Effects of aortic irregularities on blood flow

Anatomic aortic anomalies are seen in many medical conditions and are known to cause disturbances in blood flow. Turner syndrome (TS) is a genetic disorder occurring only in females where cardiovascular anomalies, particularly of the aorta, are frequently encountered. In this study, numerical simulations are applied to investigate the flow characteristics in four TS patient- related aortic arches (a normal geometry, dilatation, coarctation and elongation of the transverse aorta). The Quemada viscosity model was applied to account for the non-Newtonian behavior of blood. The blood is treated as a mixture consisting of water and red blood cells (RBC) where the RBCs are modeled as a convected scalar. The results show clear geometry effects where the flow structures and RBC distribution are significantly different between the aortas. Transitional flow is observed as a jet is formed due to a constriction in the descending aorta for the coarctation case. RBC dilution is found to vary between the aortas, influencing the WSS. Moreover, the local variations in RBC volume fraction may induce large viscosity variations, stressing the importance of accounting for the non-Newtonian effects.     

Model of cellular mechanotransduction via actin stress fibers

Mechanical stresses due to blood flow regulate vascular endothelial cell structure and function and play a key role in arterial physiology and pathology. In particular, the development of atherosclerosis has been shown to correlate with regions of disturbed blood flow where endothelial cells are round and have a randomly organized cytoskeleton. Thus, deciphering the relation between the mechanical environment, cell structure, and cell function is a key step toward understanding the early development of atherosclerosis. Recent experiments have demonstrated very rapid (\(\sim \)100 ms) and long-distance (\(\sim \)10 \(\upmu \)m) cellular mechanotransduction in which prestressed actin stress fibers play a critical role. Here, we develop a model of mechanical signal transmission within a cell by describing strains in a network of prestressed viscoelastic stress fibers following the application of a force to the cell surface. We find force transmission dynamics that are consistent with experimental results. We also show that the extent of stress fiber alignment and the direction of the applied force relative to this alignment are key determinants of the efficiency of mechanical signal transmission. These results are consistent with the link observed experimentally between cytoskeletal organization, mechanical stress, and cellular responsiveness to stress. Based on these results, we suggest that mechanical strain of actin stress fibers under force constitutes a key link in the mechanotransduction chain.     

A method for three-dimensional quantification of vascular smooth muscle orientation: application in viable murine carotid arteries

When studying in vivo arterial mechanical behaviour using constitutive models, smooth muscle cells (SMCs) should be considered, while they play an important role in regulating arterial vessel tone. Current constitutive models assume a strictly circumferential SMC orientation, without any dispersion. We hypothesised that SMC orientation would show considerable dispersion in three dimensions and that helical dispersion would be greater than transversal dispersion. To test these hypotheses, we developed a method to quantify the 3D orientation of arterial SMCs. Fluorescently labelled SMC nuclei of left and right carotid arteries of ten mice were imaged using two-photon laser scanning microscopy. Arteries were imaged at a range of luminal pressures. 3D image processing was used to identify individual nuclei and their orientations. SMCs showed to be arranged in two distinct layers. Orientations were quantified by fitting a Bingham distribution to the observed orientations. As hypothesised, orientation dispersion was much larger helically than transversally. With increasing luminal pressure, transversal dispersion decreased significantly, whereas helical dispersion remained unaltered. Additionally, SMC orientations showed a statistically significant (\(p < 0.05\)) mean right-handed helix angle in both left and right arteries and in both layers, which is a relevant finding from a developmental biology perspective. In conclusion, vascular SMC orientation (1) can be quantified in 3D; (2) shows considerable dispersion, predominantly in the helical direction; and (3) has a distinct right-handed helical component in both left and right carotid arteries. The obtained quantitative distribution data are instrumental for constitutive modelling of the artery wall and illustrate the merit of our method.     

Modeling of cell adhesion and deformation mediated by receptor–ligand interactions

The current work is devoted to studying adhesion and deformation of biological cells mediated by receptors and ligands in order to enhance the existing models. Due to the sufficient in-plane continuity and fluidity of the phospholipid molecules, an isotropic continuum fluid membrane is proposed for modeling the cell membrane. The developed constitutive model accounts for the influence of the presence of receptors on the deformation and adhesion of the cell membrane through the introduction of spontaneous area dilation. Motivated by physics, a nonlinear receptor–ligand binding force is introduced based on charge-induced dipole interaction. Diffusion of the receptors on the membrane is governed by the receptor–ligand interaction via Fick’s Law and receptor-ligand interaction. The developed model is then applied to study the deformation and adhesion of a biological cell. The proposed model is used to study the role of the material, binding, spontaneous area dilation and environmental properties on the deformation and adhesion of the cell.     

A microstructurally based continuum model of cartilage viscoelasticity and permeability incorporating measured statistical fiber orientations

The remarkable mechanical properties of cartilage derive from an interplay of isotropically distributed, densely packed and negatively charged proteoglycans; a highly anisotropic and inhomogeneously oriented fiber network of collagens; and an interstitial electrolytic fluid. We propose a new 3D finite strain constitutive model capable of simultaneously addressing both solid (reinforcement) and fluid (permeability) dependence of the tissue’s mechanical response on the patient-specific collagen fiber network. To represent fiber reinforcement, we integrate the strain energies of single collagen fibers—weighted by an orientation distribution function (ODF) defined over a unit sphere—over the distributed fiber orientations in 3D. We define the anisotropic intrinsic permeability of the tissue with a structure tensor based again on the integration of the local ODF over all spatial fiber orientations. By design, our modeling formulation accepts structural data on patient-specific collagen fiber networks as determined via diffusion tensor MRI. We implement our new model in 3D large strain finite elements and study the distributions of interstitial fluid pressure, fluid pressure load support and shear stress within a cartilage sample under indentation. Results show that the fiber network dramatically increases interstitial fluid pressure and focuses it near the surface. Inhomogeneity in the tissue’s composition also increases fluid pressure and reduces shear stress in the solid. Finally, a biphasic neo-Hookean material model, as is available in commercial finite element codes, does not capture important features of the intra-tissue response, e.g., distributions of interstitial fluid pressure and principal shear stress.     

Hydrogen production by the hyperthermophilic bacterium <Emphasis Type="Italic">Thermotoga maritima</Emphasis> part I: effects of sulfured nutriments,with thiosulfate as model,on hydrogen production and growth

Background

Thermotoga maritima and T. neapolitana are hyperthermophile bacteria chosen by many research teams to produce bio-hydrogen because of their potential to ferment a wide variety of sugars with the highest theoretical H₂/glucose yields. However, to develop economically sustainable bio-processes, the culture medium formulation remained to be optimized. The main aim of this study was to quantify accurately and specifically the effect of thiosulfate, used as sulfured nutriment model, on T. maritima growth, yields and productivities of hydrogen. The results were obtained from batch cultures, performed into a bioreactor, carefully controlled, and specifically designed to prevent the back-inhibition by hydrogen.

Results

Among sulfured nutriments tested, thiosulfate, cysteine, and sulfide were found to be the most efficient to stimulate T. maritima growth and hydrogen production. In particular, under our experimental conditions (glucose 60 mmol L^?1 and yeast extract 1 g L^?1), the cellular growth was limited by thiosulfate concentrations lower than 0.06 mmol L^?1. Under these conditions, the cellular yield on thiosulfate (Y X/Thio) could be determined at 3617 mg mmol^?1. In addition, it has been shown that the limitations of T. maritima growth by thiosulfate lead to metabolic stress marked by a significant metabolic shift of glucose towards the production of extracellular polysaccharides (EPS). Finally, it has been estimated that the presence of thiosulfate in the T. maritima culture medium significantly increased the cellular and hydrogen productivities by a factor 6 without detectable sulfide production.

Conclusions

The stimulant effects of thiosulfate at very low concentrations on T. maritima growth have forced us to reconsider its role in this species and more probably also in all thiosulfato-reducer hyperthermophiles. Henceforth, thiosulfate should be considered in T. maritima as (1) an essential sulfur source for cellular materials when it is present at low concentrations (about 0.3 mmol g^?1 of cells), and (2) as both sulfur source and detoxifying agent for H₂ when thiosulfate is present at higher concentrations and, when, simultaneously, the pH₂ is high. Finally, to improve the hydrogen production in bio-processes using Thermotoga species, it should be recommended to incorporate thiosulfate in the culture medium.

     

Large-scale production of foreign proteins via the novel plant transient expression system in <Emphasis Type="Italic">Pisum sativum</Emphasis> L.

Transient expression of foreign genes by Agrobacterium infiltration is a versatile technique that can be used as a rapid tool for functional protein production in plants. A reproducible protocol of large-scale production of foreign proteins via the novel plant transient expression system in Pisum sativum L. was established in our study. Non-detached plants from soil-independent culture were used as the target organ, and vacuum infiltrating mediated by Agrobacterium tumefaciens harboring green fluorescent protein (GFP) gene was performed. Step-by-step optimization was performed and showed that the quality of plant material as well as agro-infiltration conditions were the major factors influencing the gene expression. Monitoring the transient GFP expression daily, the highest expression level was achieved on the 8th day post-infiltration. Evidence of anti-acidic fibroblast growth factor-single chain variable fragment (anti-aFGF-scFv) gene expression in pea seedling was also achieved using agro-mediated vacuum infiltration system. Our work proves that the system is suitable for the largescale production of pharmaceutical proteins. The in planta infiltration system described here provides a powerful tool to explore easily gene expression in Pisum sativum L. avoiding tissue culture steps and the labor-intensive generation of transgenic plants.