Mechanics & chemistry of biosystems : MCB最新文献

Alpha-actinin, an actin binding protein, plays a key role in cell migration, cross-links actin filaments in the Z-disk, and is a major component of contractile muscle apparatus. The flexibility of the molecule is critical to its function. The flexibility of various regions of the molecule, including the linker connecting central subunits is studied using constant force steered molecular dynamics simulations. The linker, whose structure has been a subject of debate, is predicted to be semi-flexible. The flexibility of the linker is compared to all possible segments of equal length throughout the molecule. The stretching profile of the molecule at different forces suggests that loops and regions adjacent to the loops are much more rigid than the helices in the protein. Amino acid composition analysis of most flexible and most rigid regions of the molecule reveals that the rigid regions are rich in Ser, Val and Ile whereas the flexible regions are rich in Ala, Leu and Glu.

The Bcl-2 family of proteins has recently been implicated as a possible player in the complex cascade of neural cell death due to traumatic brain injuries. However, it is unclear if the Bcl-2 pathways are activated in mechanically injured neurons. Here we report the effects of BclX(L) and Bax over-expression on stretch-induced neural cell death using an in vitro uniaxial stretch model of traumatic axonal injury. Specifically, YFP, YFP-tagged Bax and YFP-tagged BclX(L) proteins were expressed in differentiated NG108-15 cells and stretch-injury assays were carried out at different strain and strain rate combinations. As a control, insults known to act within the Bcl-2 pathways were used to study cell viability and to compare with the results of cell death due to mechanical stretching. Surprisingly, under the stretch-injury conditions in this study, BclXL did not provide protection against cell death. Further, translocation of Bax could not be identified after stretch-injury. The implications of these findings to cell death pathways in traumatic brain injury are discussed.

Although it is established that endothelial cells can respond to external mechanical cues (e.g., alignment in the direction of fluid shear stress), the extent to which mechanical stress and strain applied via the endothelial cell substrate impact biomolecular and cellular processes is not well-understood. This issue is particularly important in the context of inflammation, vascular remodeling, and cancer progression, as each of these processes occurs concurrently with localized increases in strain and marked changes in molecules secreted by adjacent cells. Here, we systematically vary the level and duration of cyclic tensile strain applied to human dermal microvascular and bovine capillary endothelial cells via substrate deflection, and then correlate these cues with the secretion of extracellular matrix-degrading enzymes and a morphological transition from confluent monolayers to well-defined multicellular networks that resemble capillary tube-like structures. For a constant chemical environment, we find that super-physiological mechanical strain stimulates both endothelial cell secretion of latent matrix metalloprotease-2 and multicellular networks in a time- and strain-dependent manner. These results demonstrate coupling between the mechanical and biochemical states of microvascular endothelial cells, and indicate that elevated local stress may directly impact new capillary growth (angiogenesis) toward growing tumors and at capillary wall defect sites.

In recent single-particle tracking (SPT) measurements on Listeria monocytogenes motility in cells [Kuo and McGrath (2000)], the actin-based stochastic dynamics of the bacterium movement has been analyzed statistically in terms of the mean-square displacement (MSD) of the trajectory. We present a stochastic analysis of a simplified polymerization Brownian ratchet (BR) model in which motions are limited by the bacterium movement. Analytical results are obtained and statistical data analyses are investigated. It is shown that the MSD of the stochastic bacterium movement is a monotonic quadratic function while the MSD for detrended trajectories is linear. Both the short-time relaxation and the long-time kinetics in terms the mean velocity and effective diffusion constant of the propelled bacterium are obtained from the MSD analysis. The MSD of the gap between actin tip and the bacterium exhibits an oscillatory behavior when there is a large resistant force from the bacterium. For comparison, a continuous diffusion formalism of the BR model with great analytical simplicity is also studied.

Membrane-bound integrin receptors are linked to intracellular signaling pathways through focal adhesion kinase (FAK). FAK tends to colocalize with integrin receptors at focal adhesions through its C-terminal focal adhesion targeting (FAT) domain. Through recruitment and binding of intracellular proteins, FAs transduce signals between the intracellular and extracellular regions that regulate a variety of cellular processes including cell migration, proliferation, apoptosis and detachment from the ECM. The mechanism of signaling through the cell is of interest, especially the transmission of mechanical forces and subsequent transduction into biological signals. One hypothesis relates mechanotransduction to conformational changes in intracellular proteins in the force transmission pathway, connecting the extracellular matrix with the cytoskeleton through FAs. To assess this hypothesis, we performed steered molecular dynamics simulations to mechanically unfold FAT and monitor how force-induced changes in the molecular conformation of FAT affect its binding to paxillin.

Flow dynamics play an important role in the pathogenesis and treatment of intracranial aneurysms. The evaluation of the velocity field in the aneurysm dome and neck is important for the correct placement of endovascular coils, and the temporal and spatial variations of wall shear stress in the aneurysm are correlated with its growth and rupture. This numerical investigation describes the hemodynamic in two models of terminal aneurysm of the basilar artery. Aneurysm models with a aspect ratio of 1.0 and 1.67 were studied. Each model was subject to physiological representative waveform of inflow for a mean Reynolds number of 560. The effects of symmetric and asymmetric outflow conditions in the branches were studied. The three dimensional continuity and Navier-Stokes equations for incompressible, unsteady laminar flow with Newtonian properties were solved with a commercial software using non structured fine grids with 197807 and 202515 tetrahedral cells for the model 1 and 2 respectively. The flow shows complex vortex structure in both models, the inflow and outflow zones in the aneurysm neck were determined. The wall shear stress on the aneurysm showed big temporal and spatial variations. The asymmetric outflow increased the wall shear stress on the aneurysm only in model 1.

During the last decades, it has become increasingly common to make balloons distension in visceral organs in vivo. In particular this is true for studies of gastrointestinal motor function and biomechanics. Balloon distension is often used for assessment of small intestinal compliance and tension based on Laplace's law for cylindrical pressure pipes. This commonly used law is valid only when the balloon-distended intestine is cylindrical. Experimentally, it is seen that the diameter of the balloon-distended intestine is not a constant, but variable in the axial direction. Hence, it is necessary to improve Laplace's law for intestinal investigation. In this paper we develop the framework for determination of the tension distribution in circumferential and longitudinal direction during balloon distension. When the radii of curvature are measured from a photograph of the intestinal profile, then the membrane stress resultants can be computed everywhere in the intestine in contact with the balloon from the equations of equilibrium. The experimental data were obtained from small intestinal segments from five pigs and three guinea pigs. Papaverine was injected before the animals were sacrificed to relax the intestinal smooth muscle. The segments were immersed in a bath with calcium-free Krebs solution with dextran and EGTA. A balloon was distended in the lumen with pressures up to 15 cmH2O in the pigs and 10 cmH2O in the guinea pigs and radii were measured along the z-axis. The tension in circumferential direction had its maximum approximately 25% away from the middle of the balloon. The circumferential tension was 2-3 times higher than the longitudinal tension. In conclusion when we know the shape of the intestine, we can compute the circumferential and longitudinal components of tension. The large variation in tensions along the z axis must be considered when performing balloon distension studies in the gastrointestinal tract for studying physiological and pathophysiological problems in which loading conditions are important, e.g. intestinal mechanoreceptor studies in order to obtain accurate description of the biomechanics and the stimulus-response function.