Martin Kroon

A calcium-driven mechanochemical model for prediction of force generation in smooth muscle

A new model for the mechanochemical response of smooth muscle is presented. The focus is on the res- ponse of the actin–myosin complex and on the related generation of force (or stress). The chemical (kinetic) model describes the cross-bridge interactions with the thin filament in which the calcium-dependent myosin phosphorylation is the only regulatory mechanism. The new mechanical model is based on Hill’s three-component model and it includes one internal state variable that describes the contraction/relaxation of the contractile units. It is characterized by a strain-energy function and an evolution law incorporating only a few material parameters with clear physical meaning. The proposed model satisfies the second law of thermodynamics. The results of the combined coupled model are broadly consistent with isometric and isotonic experiments on smooth muscle tissue. The simulations suggest that the matrix in which the actin–myosin complex is embedded does have a viscous property. It is straightforward for implementation into a finite element program in order to solve more complex boundary-value problems such as the control of short-term changes in lumen diameter of arteries due to mechanochemical signals.

A new constitutive model for multi-layered collagenous tissues.

Collagenous tissues such as the aneurysmal wall or the aorta are multi-layered structures with the mean fibre alignments distinguishing one layer from another. A constitutive representation of the multiple collagen layers is not yet developed, and hence the aim of the present study. The proposed model is based on the constitutive theory of finite elasticity and is characterized by an anisotropic strain-energy function which takes the material structure into account. The passive tissue behaviour is modelled and the related mechanical response is assumed to be dominated by elastin and collagen. While elastin is modelled by the neo-Hookean material the constitutive response of collagen is assumed to be transversely isotropic for each individual layer and based on an exponential function. The proposed constitutive function is polyconvex which ensures material stability. The model has five independent material parameters, each of which has a clear physical interpretation: the initial stiffnesses of the collagen fabric in the two principal directions, the shear modulus pertaining to the non-collagenous matrix material, a parameter describing the level of nonlinearity of the collagen fabric, and the angle between the principal directions of the collagen fabric and the reference coordinate system. An extension-inflation test of the adventitia of a human femoral artery is simulated by means of the finite element method and an error function is minimized by adjusting the material parameters yielding a good agreement between the model and the experimental data.

A probabilistic model for cleavage fracture with a length scale - parameter estimation and predictions of stationary crack experiments

This study presents a large experimental investigation in the transition temperature region on a modified A508 steel. Tests were carried out on single-edge-notch-bend specimens with three different ...

A theoretical model for fibroblast-controlled growth of saccular cerebral aneurysms

A new theoretical model for the growth of saccular cerebral aneurysms is proposed by extending the recent constitutive framework of Kroon and Holzapfel [2007a. A model for saccular cerebral aneurysm growth by collagen fibre remodelling. J. Theor. Biol. 247, 775-787]. The continuous turnover of collagen is taken to be the driving mechanism in aneurysmal growth. The collagen production rate depends on the magnitude of the cyclic deformation of fibroblasts, caused by the pulsating blood pressure during the cardiac cycle. The volume density of fibroblasts in the aneurysmal tissue is taken to be constant throughout the growth process. The growth model is assessed by considering the inflation of an axisymmetric membranous piece of aneurysmal tissue, with material characteristics representative of a cerebral aneurysm. The diastolic and systolic states of the aneurysm are computed, together with its load-free state. It turns out that the value of collagen pre-stretch, that determines growth speed and stability of the aneurysm, is of pivotal importance. The model is able to predict aneurysms with typical berry-like shapes observed clinically, and the predicted wall stresses correlate well with the experimentally obtained ultimate stresses of this type of tissue. The model predicts that aneurysms should fail when reaching a size of about 1.2-3.6mm, which is smaller than what has been clinically observed. With some refinements, the model may, however, be used to predict future growth of diagnosed aneurysms.

A probabilistic model for cleavage fracture with a length scale : influence of material parameters and constraint

A probabilistic model for the cumulative probability of failure by cleavage fracture with a material related length scale is developed in this study. The model aims at describing the random nature of fracture in ferritic steels in the brittle-to-ductile transition temperature region. The model derives from use of an exponential function to describe the distribution of microstructural entities eligible to take part in the fracture initiation process, where also a dependence on effective plastic strain is incorporated. A nonlocal stress measure, calculated as the average stress in a spherical volume, drives the contribution to failure probability of an infinitesimal material volume. The radius of the spherical volume enters as the material length in this model. This length has a significant influence on failure probability predictions in geometries exposed to strong stress gradients as found ahead of cracks. The material length is associated with a fracture toughness threshold value. In a fracture application three model parameters need to be estimated based on testing; a parameter directly related to the mean fracture toughness, a parameter that primarily is related to crack-tip constraint effects and the material length parameter. The model is explored in a parametric study showing model features in concord with typical features found in toughness distributions from fracture mechanics testing in the transition region.

Estimation of the distributions of anisotropic, elastic properties and wall stresses of saccular cerebral aneurysms by inverse analysis

A new method is proposed for estimating the elastic properties of the inhomogeneous and anisotropic structure of saccular cerebral aneurysms by inverse analysis. The aneurysm is modelled as a membrane and the constitutive response of each individual layer of the passive tissue is characterized by a transversely isotropic strain energy function of exponential type. The collagen fibres in the aneurysm wall are assumed to govern the mechanical response. Four parameters characterize the constitutive behaviour of the tissue: two initial stiffnesses of the collagen fabric in the two in-plane principal directions, one parameter describing the degree of nonlinearity that the collagen fibres exhibit and the other structural parameter, i.e. the angle which defines the orientation of the collagen fibres. The parameter describing the fibre nonlinearity is assumed to be constant, while all others are assumed to vary continuously over the aneurysm surface. Two model aneurysms, with the same initial geometry, boundary and loading conditions, constitutive behaviour and finite-element discretization, are defined: a ‘reference model’ with known distributions of material and structural properties and an ‘estimation model’ whose properties are to be estimated. An error function is defined quantifying the deviations between the deformations from the reference and the estimation models. The error function is minimized with respect to the unknown parameters in the estimation model, and in this way the reference parameter distributions are re-established. In order to achieve a robust parameter estimation, a novel element partition method is employed. The accordance between the estimated and the reference distributions is satisfactory. The deviations of the maximum stress distributions between the two models are below 1%. Consequently, the wall stresses in the cerebral aneurysm estimated by inverse analysis are accurate enough to facilitate the assessment of the risk of aneurysm rupture.

A constitutive model for smooth muscle including active tone and passive viscoelastic behaviour

A new constitutive model for the biomechanical behaviour of smooth muscle tissue is proposed. The active muscle contraction is accomplished by the relative sliding between actin and myosin filaments, comprising contractile units in the smooth muscle cells. The model includes a chemical part, governing the cross-bridge (myosin head) cycling, that is responsible for the filament sliding. The number of activated cross-bridges govern the contractile force generated and also the contraction speed. A strain-energy function is used to describe the mechanical behaviour of the smooth muscle tissue. Besides the active contractile apparatus, the mechanical model also incorporates a passive viscoelastic part. The constitutive model was calibrated with respect to experiments on smooth muscle tissue from swine carotid artery and guinea pig taenia coli, in terms of isometric and isotonic tensile test results. The model was fully able to reproduce the experimental results.

Numerical analysis of dynamic crack propagation in rubber

In the present paper, dynamic crack propagation in rubber is analyzed numerically using the finite element method. The problem of a suddenly initiated crack at the center of stretched sheet is studied under plane stress conditions. A nonlinear finite element analysis using implicit time integration scheme is used. The bulk material behavior is described by finite-viscoelasticity theory and the fracture separation process is characterized using a cohesive zone model with a bilinear traction-separation law. Hence, the numerical model is able to model and predict the different contributions to the fracture toughness, i.e. the surface energy, viscoelastic dissipation, and inertia effects. The separation work per unit area and the strength of the cohesive zone have been parameterized, and their influence on the separation process has been investigated. A steadily propagating crack is obtained and the corresponding crack tip position and velocity history as well as the steady crack propagation velocity are evaluated and compared with experimental data. A minimum threshold stretch of 3.0 is required for crack propagation. The numerical model is able to predict the dynamic crack growth. It appears that the strength and the surface energy vary with the crack speed. Finally, the maximum principal stretch and stress distribution around steadily propagation crack tip suggest that crystallization and cavity formation may take place.

Experimental and computational assessment of F-actin influence in regulating cellular stiffness and relaxation behaviour of fibroblasts

In biomechanics, a complete understanding of the structures and mechanisms that regulate cellular stiffness at a molecular level remain elusive. In this paper, we have elucidated the role of filamentous actin (F-actin) in regulating elastic and viscous properties of the cytoplasm and the nucleus. Specifically, we performed colloidal-probe atomic force microscopy (AFM) on BjhTERT fibroblast cells incubated with Latrunculin B (LatB), which results in depolymerisation of F-actin, or DMSO control. We found that the treatment with LatB not only reduced cellular stiffness, but also greatly increased the relaxation rate for the cytoplasm in the peripheral region and in the vicinity of the nucleus. We thus conclude that F-actin is a major determinant in not only providing elastic stiffness to the cell, but also in regulating its viscous behaviour. To further investigate the interdependence of different cytoskeletal networks and cell shape, we provided a computational model in a finite element framework. The computational model is based on a split strain energy function of separate cellular constituents, here assumed to be cytoskeletal components, for which a composite strain energy function was defined. We found a significant influence of cell geometry on the predicted mechanical response. Importantly, the relaxation behaviour of the cell can be characterised by a material model with two time constants that have previously been found to predict mechanical behaviour of actin and intermediate filament networks. By merely tuning two effective stiffness parameters, the model predicts experimental results in cells with a partly depolymerised actin cytoskeleton as well as in untreated control. This indicates that actin and intermediate filament networks are instrumental in providing elastic stiffness in response to applied forces, as well as governing the relaxation behaviour over shorter and longer time-scales, respectively.

Modelling of cross-linked actin networks - Influence of geometrical parameters and cross-link compliance

A major structural component of the cell is the actin cytoskeleton, in which actin subunits are polymerised into actin filaments. These networks can be cross-linked by various types of ABPs (Actin Binding Proteins), such as Filamin A. In this paper, the passive response of cross-linked actin filament networks is evaluated, by use of a numerical and continuum network model. For the numerical model, the influence of filament length, statistical dispersion, cross-link compliance (including that representative of Filamin A) and boundary conditions on the mechanical response is evaluated and compared to experimental results. It is found that the introduction of statistical dispersion of filament lengths has a significant influence on the computed results, reducing the network stiffness by several orders of magnitude. Actin networks have previously been shown to have a characteristic transition from an initial bending-dominated to a stretching-dominated regime at larger strains, and the cross-link compliance is shown to shift this transition. The continuum network model, a modified eight-chain polymer model, is evaluated and shown to predict experimental results reasonably well, although a single set of parameters cannot be found to predict the characteristic dependence of filament length for different types of cross-links. Given the vast diversity of cross-linking proteins, the dependence of mechanical response on cross-link compliance signifies the importance of incorporating it properly in models to understand the roles of different types of actin networks and their respective tasks in the cell.