Fibrillins, fibulins, and matrix-associated glycoprotein modulate the kinetics and morphology of in vitro self-assembly of a recombinant elastin-like polypeptide

Elastin is the polymeric protein responsible for the properties of extensibility and elastic recoil of the extracellular matrix in a variety of tissues. Although proper assembly of the elastic matrix is crucial for its durability, the process by which this assembly takes place is not well-understood. Recent data suggest the complex interaction of tropoelastin, the monomeric form of elastin, with a number of other elastic matrix-associated proteins, including fibrillins, fibulins, and matrix-associated glycoprotein (MAGP), is important to achieve the proper architecture of the elastic matrix. At the same time, it is becoming clear that self-assembly properties intrinsic to tropoelastin itself, reflected in a temperature-induced phase separation known as coacervation, are also important in this assembly process. In this study, using a well-characterized elastin-like polypeptide that mimics the self-assembly properties of full-length tropoelastin, the process of self-assembly is deconstructed into "coacervation" and "maturation" stages that can be distinguished kinetically by different parameters. Members of the fibrillin, fibulin, and MAGP families of proteins are shown to profoundly affect both the kinetics of self-assembly and the morphology of the maturing coacervate, restricting the growth of coacervate droplets and, in some cases, causing clustering of droplets into fibrillar structures.     

A time-dependent healing function for immediate loaded implants

Current interest in immediate dental implant loading has grown due to a number of clinical advantages this treatment modality offers. To obtain a deeper insight into the changing mechanical properties during the healing phase, results from removal torque tests are used in a biomechanical model. The ultimate removal torques, which depend on healing time, are described by a time-dependent healing function. The bone behavior is modeled using an elastic law with damage. The evolution of damage is represented with an incremental equation with an initial damage value and two material parameters. The nonlinear relationship between the torque and the angle of rotation up to the ultimate torque can be calculated. By changing the elastic parameter in the elastic damage law, the remodeling process can be characterized. In a further step, the elastic parameters and the limits for shear stress from the biomechanical model for the removal torque will be used in an FE analysis in order to obtain information on the axial loading limits of a dental implant at different healing times.     

Effects of physical exercise on the elasticity and elastic components of the rat aorta

To evaluate the effects of exercise on aortic wall elasticity and elastic components, young male rats underwent various exercise regimes for 16 weeks. In the exercised rats, the aortic incremental elastic modulus decreased significantly when under physiological strain. The aortic content of elastin increased significantly and the calcium content of elastin decreased significantly in the exercised group. The accumulated data from the exercised and sedentary groups revealed that the elastin calcium content was related positively to the incremental elastic modulus. We concluded that physical exercise from an early age decreases the calcium deposit in aortic wall elastin and that this effect probably produced in the exercised rats a distensible aorta.     

Analysis of the passive mechanical properties of rat carotid arteries

The passive mechanical properties of rat carotid arteries were studied in vitro. Using a tensile testing machine and a piston pump, intact segments of carotid arteries were subjected to large deformations both in the longitudinal and circumferential directions. Internal pressure, external diameter, length and longitudinal force were measured during the experiment and compared with the in vivo dimensions of the segments prior to excision. The anisotropic mechanical properties of the vessel wall material were analyzed using incremental elastic moduli and incremental Poisson's ratios. The results suggest that there is a characteristic deformation pattern common to all vessels investigated which is highly correlated with the conditions of loading that occur in vivo. That is, under average physiological deformation of the vessel, the longitudinal force is nearly independent of internal pressure. In this range of loading the circumferential incremental elastic modulus is nearly independent of longitudinal strain. However, the longitudinal and radial incremental elastic moduli vary significantly with deformation in this direction. The values of the moduli in all three directions increase with raising internal pressure. The weak coupling between circumferential and longitudinal direction in the wall material of carotid arteries is shown by the small value of the corresponding incremental Poisson's ratios.     

Connecting incremental shear modulus and Poisson's ratio of lung tissue with morphology and rheology of microstructure

The width and curvature of the collagen and elastin fiber bundles in the human pulmonary interalveolar septa and alveolar mouths are measured. The data, together with the known mechanical properties of collagen and elastin fibers, are used to derive the incremental elastic moduli of the lung tissue. The constitutive equation for small incremental stress and strain superposed on a homeostatic inflated lung is linear and isotropic, and characterized by two material constants.     

In vitro effects of elastase on periosteum of long bones: an histochemical, immunohistochemical and morphometric study

The aim of the study was to determine the in vitro effects of porcine pancreatic elastase on the periosteum of long bones and to what extent the effects are selective for the elastic fibres of the tissue. Twenty-eight new-born chicks' tibiae were incubated for 1 or 3 hours in different experimental conditions (PBS, 30 or 60 units (U)/ml of porcine pancreatic elastase) or immediately formalin fixed. The tibiae were then processed for histo-chemical (Verhoeff and van Gieson stain), immunohistochemical (anti-elastin antibody) and histomorphometric analysis. A decrease of periosteal elastic fibres in all the specimens incubated with elastase in comparison with non incubated specimens was evident. The effect of elastase was easily detectable even at the lower concentration (30 U/ml) and at the shorter time of incubation (1 h). The amount of elastic fibres decreased in accordance with the rise of enzyme levels and incubation time, while periosteal collagen fibre content was not substantially modified by elastase activity. Present data are a prerequisite to evaluate the in vitro and in vivo effects of experimental destruction of periosteal elastic fibres by elastase and to assess the role of these fibres in the growth process of long bones.     

Stress generation,relaxation and size control in confined tumor growth

Experiments on tumor spheroids have shown that compressive stress from their environment can reversibly decrease tumor expansion rates and final sizes. Stress release experiments show that nonuniform anisotropic elastic stresses can be distributed throughout. The elastic stresses are maintained by structural proteins and adhesive molecules, and can be actively relaxed by a variety of biophysical processes. In this paper, we present a new continuum model to investigate how the growth-induced elastic stresses and active stress relaxation, in conjunction with cell size control feedback machinery, regulate the cell density and stress distributions within growing tumors as well as the tumor sizes in the presence of external physical confinement and gradients of growth-promoting chemical fields. We introduce an adaptive reference map that relates the current position with the reference position but adapts to the current position in the Eulerian frame (lab coordinates) via relaxation. This type of stress relaxation is similar to but simpler than the classical Maxwell model of viscoelasticity in its formulation. By fitting the model to experimental data from two independent studies of tumor spheroid growth and their cell density distributions, treating the tumors as incompressible, neo-Hookean elastic materials, we find that the rates of stress relaxation of tumor tissues can be comparable to volumetric growth rates. Our study provides insight on how the biophysical properties of the tumor and host microenvironment, mechanical feedback control and diffusion-limited differential growth act in concert to regulate spatial patterns of stress and growth. When the tumor is stiffer than the host, our model predicts tumors are more able to change their size and mechanical state autonomously, which may help to explain why increased tumor stiffness is an established hallmark of malignant tumors.     

Theoretical analysis of the effect of the transbilayer movement of phospholipid molecules on the dynamic behavior of a microtube pulled out of an aspirated vesicle

Observations over extended times of a lipid microtube (tether) formed from a lecithin vesicle have shown that under constant external loads the tether exhibits a continuous slow growth. It is considered that this growth is a consequence of the net transbilayer movement of phospholipid molecules in a direction which relieves the membrane strain resulting from the elastic deformation of the vesicle. The elastic deformation mode responsible for this effect is identified as the relative expansion of the two membrane layers reflecting the non-local contribution to membrane bending. An equation for the consequent rate of transbilayer movement of phospholipid molecules is derived. The dynamic behavior of the system is modeled by including frictional contributions due to interlayer slip and Stokes drag on the glass bead used to form the tether. The general numerical solution reveals a complex dependence of the tether growth rate on the system parameters and a continuous increase in the rate of tether growth at long times. Closed form expressions approximating the system behavior are derived and the conditions under which they can be applied are specified. Modeling the mechanically-driven lipid transport as a simple, stochastic, thermal process, allows the rate of lipid translocation to be related to the equilibrium transbilayer exchange rate of phospholipid molecules. Consideration of experimental results shows that the time constant for mechanically-driven translocation is shorter than the time for diffusion-driven translocation by approximately two orders of magnitude, indicating that lipid translocation is not a simple diffusive process. Received: 29 November 1996 / Revised version: 1 December 1997 / Accepted: 9 January 1998     

How the microstructure of dentine can contribute to reconstructing developing dentitions and the lives of hominoids and hominins

Accounts of dentine microstructure are less well established in the primate life history literature than those of enamel microstructure. The aim of this paper is to draw some basic comparisons between enamel and dentine, but at the same time to show how dentine microstructure can make a major but different contribution to reconstructing past lives than enamel can. Dentine has both an organic and an inorganic component. The organic component contains growth factors, stable isotopes and DNA that survive long after death. The mineral component contains trace elements and preserves an incremental record of tooth growth. These can be used to put a time scale to many past events when the chemistry or microstructure of dentine has become altered during tooth growth. Dentine microstructure allows us to reconstruct tooth root growth in the past and has contributed to a fuller understanding of the modular nature of developing dentitions among hominoids and hominins.     

Numerical study of how creep and progressive stiffening affect the growth stress formation in trees

It is not fully understood how much growth stresses affect the final quality of solid timber products in terms of, e.g. shape stability. It is, for example, difficult to predict the internal growth stress field within the tree stem. Growth stresses are progressively generated during the tree growth and they are highly influenced by climate, biologic and material-related factors. To increase the knowledge of the stress formation, a finite element model was created to study how the growth stresses develop during the tree growth. The model is an axisymmetric general plane strain model where material for all new annual rings is progressively added to the tree during the analysis. The material model used is based on the theory of small strains (where strains refer to the undeformed configuration which is good approximation for strains less than 4%) where so-called biological maturation strains (growth-related strains that form in the wood fibres during their maturation) are used as a driver for the stress generation. It is formulated as an incremental material model that takes into account elastic strain, maturation strain, viscoelastic strain and progressive stiffening of the wood material. The results clearly show how the growth stresses are progressively generated during the tree growth. The inner core becomes more and more compressed, whereas the outer sapwood is subjected to slightly increased tension. The parametric study shows that the growth stresses are highly influenced by the creep behaviour and evolution of parameters such as modulus of elasticity, micro-fibril angle and maturation strain.     

Turgor, temperature and the growth of plant cells: using Chara corallina as a model system

Rapid changes in turgor pressure (P:) and temperature (T:) are giving new information about the mechanisms of plant growth. In the present work, single internode cells of the large-celled alga Chara corallina were used as a model for plant growth. P was changed without altering the chemical environment of the wall while observing growth without elastic changes. When P: was measured before any changes, the original growth rate bore no relationship to the original P. However, if P of growing cells was decreased, growth responded immediately without evidence for rapid changes in wall physical properties. Growth occurred only above a 0.3 MPa threshold, and increasing P caused small increases in growth that became progressively larger as P rose, resulting in a curvilinear response overall. The small changes in growth close to the threshold may explain early failures to detect these responses. When T was lowered, the elastic properties of the cell were unaffected, but growth was immediately inhibited. The lower T caused P to decrease, but returning P to its original value did not return growth to its original rate. The decreased P at low T occurred because of T effects on the osmotic potential of the cell. At above-normal P, growth partially resumed at low T Therefore, growth required a P-sensitive process that was also T-sensitive. Because elastic properties were little affected by T, but growth was markedly affected, the process is likely to involve metabolism. The rapidity of its response to P and T probably excludes the participation of changes in gene expression.