Numerical analysis of the impact of cytoskeletal actin filament density alterations onto the diffusive vesicle-mediated cell transport.

The interior of a eukaryotic cell is a highly complex composite material which consists of water, structural scaffoldings, organelles, and various biomolecular solutes. All these components serve as obstacles that impede the motion of vesicles. Hence, it is hypothesized that any alteration of the cytoskeletal network may directly impact or even disrupt the vesicle transport. A disruption of the vesicle-mediated cell transport is thought to contribute to several severe diseases and disorders, such as diabetes, Parkinson's and Alzheimer's disease, emphasizing the clinical relevance. To address the outlined objective, a multiscale finite element model of the diffusive vesicle transport is proposed on the basis of the concept of homogenization, owed to the complexity of the cytoskeletal network. In order to study the microscopic effects of specific nanoscopic actin filament network alterations onto the vesicle transport, a parametrized three-dimensional geometrical model of the actin filament network was generated on the basis of experimentally observed filament densities and network geometries in an adenocarcinomic human alveolar basal epithelial cell. Numerical analyzes of the obtained effective diffusion properties within two-dimensional sampling domains of the whole cell model revealed that the computed homogenized diffusion coefficients can be predicted statistically accurate by a simple two-parameter power law as soon as the inaccessible area fraction, due to the obstacle geometries and the finite size of the vesicles, is known. This relationship, in turn, leads to a massive reduction in computation time and allows to study the impact of a variety of different cytoskeletal alterations onto the vesicle transport. Hence, the numerical simulations predicted a 35% increase in transport time due to a uniformly distributed four-fold increase of the total filament amount. On the other hand, a hypothetically reduced expression of filament cross-linking proteins led to sparser filament networks and, thus, a speed up of the vesicle transport.

Experimental and mathematical characterization of coronary polyamide-12 balloon catheter membranes.

The experimental quantification and modeling of the multiaxial mechanical response of polymer membranes of coronary balloon catheters have not yet been carried out. Due to the lack of insights, it is not shown whether isotropic material models can describe the material response of balloon catheter membranes expanded with nominal or higher, supra-nominal pressures. Therefore, for the first time, specimens of commercial polyamide-12 balloon catheters membranes were investigated during uniaxial and biaxial loading scenarios. Furthermore, the influence of kinematic effects on the material response was observed by comparing results from quasi-static and dynamic biaxial extension tests. Novel clamping techniques are described, which allow to test even tiny specimens taken from the balloon membranes. The results of this study reveal the semi-compliant, nonlinear, and viscoelastic character of polyamide-12 balloon catheter membranes. Above nominal pressure, the membranes show a pronounced anisotropic mechanical behavior with a stiffer response in the circumferential direction. The anisotropic feature intensifies with an increasing strain-rate. A modified polynomial model was applied to represent the realistic mechanical response of the balloon catheter membranes during dynamic biaxial extension tests. This study also includes a compact set of constitutive model parameters for the use of the proposed model in future finite element analyses to perform more accurate simulations of expanding balloon catheters.

Quantification of Shear Deformations and Corresponding Stresses in the Biaxially Tested Human Myocardium.

One goal of cardiac research is to perform numerical simulations to describe/reproduce the mechanoelectrical function of the human myocardium in health and disease. Such simulations are based on a complex combination of mathematical models describing the passive mechanical behavior of the myocardium and its electrophysiology, i.e., the activation of cardiac muscle cells. The problem in developing adequate constitutive models is the shortage of experimental data suitable for detailed parameter estimation in specific functional forms. A combination of shear and biaxial extension tests with different loading protocols on different specimen orientations is necessary to capture adequately the direction-dependent (orthotropic) response of the myocardium. In most experimental animal studies, where planar biaxial extension tests on the myocardium have been conducted, the generated shear stresses were neither considered nor discussed. Hence, in this study a method is presented which allows the quantification of shear deformations and related stresses. It demonstrates an approach for experimenters as to how the generation of these shear stresses can be minimized during mechanical testing. Experimental results on 14 passive human myocardial specimens, obtained from nine human hearts, show the efficiency of this newly developed method. Moreover, the influence of the clamping technique of the specimen, i.e., the load transmission between the testing device and the tissue, on the stress response is determined by testing an isotropic material (Latex). We identified that the force transmission between the testing device and the specimen by means of hooks and cords does not influence the performed experiments. We further showed that in-plane shear stresses definitely exist in biaxially tested human ventricular myocardium, but can be reduced to a minimum by preparing the specimens in an appropriate manner. Moreover, we showed whether shear stresses can be neglected when performing planar biaxial extension tests on fiber-reinforced materials. The used method appears to be robust to quantify normal and shear deformations and corresponding stresses in biaxially tested human myocardium. This method can be applied for the mechanical characterization of any fiber-reinforced material using planar biaxial extension tests.