A multilayered model of the aortic wall is introduced to investigate the transport of low-density lipoprotein (LDL) under hypertension, taking into account the influences of increased endothelial cell turnover and deformation of the intima at higher pressure. Meanwhile, the thickness and properties of the endothelium, intima, internal elastic lamina (IEL), and media are affected by the transmural pressure. The LDL macromolecules enter the intima through leaky junctions over the endothelium, which are created by dying or dividing cells. Water molecules enter the intima via the paracellular pathway through breaks in tight junctions after passing the glycocalyx as well as through leaky junctions. The glycocalyx is modeled as a Brinkman porous medium to describe the fluid filtration associated with its structure. Combined Navier-Stokes and Brinkman equations are solved for the transmural flow, and the convective-diffusion equation is employed for LDL transport. The permeation of LDL over the surface of smooth muscle cells is modeled through a uniform reaction evenly distributed in the macroscopically homogeneous media layer. Simulations are performed in an axisymmetric plane centered at a leaky cell. The overriding issue addressed is that LDL fluxes across the leaky junction, the intima, fenestral pores in the IEL, and the media layer are highly affected by the transmural pressure, which affects the endothelial cell turnover rate and the compaction of intima. The present model, for the first time and with no adjustable parameters, is capable of making many realistic predictions including the proper magnitudes for the permeability of endothelium and intimal layers and the hydraulic conductivity of all layers as well as their trends with pressure. Results for the volume flux through the wall and the hydraulic conductivity of the entire arterial wall, the endothelium, and subendothelial layers at 70 and 180 mmHg are in good agreement with previous experimental studies.

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A three-dimensional computer model of human aortic arch with three branches is reproduced to study the pulsatile blood flow with Finite Element Method. In specific, the focus is on variation of wall shear stress, which plays an important role in the localization and development of atherosclerotic plaques. Pulsatile pressure pulse is used as boundary condition to avoid flow entry development, and the aorta walls are considered rigid. The aorta model along with boundary conditions is altered to study the effect of hypotension and hypertension. The results illustrated low and fluctuating shear stress at outer and inner wall of aortic arch, proximal wall of branches, and entry region. Despite the simplification of aorta model, rigid walls and other assumptions results displayed that hypertension causes lowered local wall shear stresses. It is the sign of an increased risk of atherosclerosis. The assessment of hemodynamics shows that under the flow regimes of hypotension and hypertension, the risk of atherosclerosis localization in human aorta may increase.

Local haemodynamics are linked to the non-uniform distribution of atherosclerosic lesions in arteries. Low and oscillatory (reversing in the axial flow direction) wall shear stress (WSS) induce inflammatory responses in endothelial cells (ECs) mediating disease localization. The objective of this study is to investigate computationally how the flow direction (reflected in WSS variation on the EC surface over time) influences the forces experienced by structural components of ECs that are believed to play important roles in mechanotransduction. A three-dimensional, multi-scale, multi-component, viscoelastic model of focally adhered ECs is developed, in which oscillatory WSS (reversing or non-reversing) parallel to the principal flow direction, or multi-directional oscillatory WSS with reversing axial and transverse components are applied over the EC surface. The computational model includes the glycocalyx layer, actin cortical layer, nucleus, cytoskeleton, focal adhesions (FAs), stress fibres and adherens junctions (ADJs). We show the distinct effects of atherogenic flow profiles (reversing unidirectional flow and reversing multi-directional flow) on subcellular structures relative to non-atherogenic flow (non-reversing flow). Reversing flow lowers stresses and strains due to viscoelastic effects, and multi-directional flow alters stress on the ADJs perpendicular to the axial flow direction. The simulations predict forces on integrins, ADJ filaments and other substructures in the range that activate mechanotransduction.

Haemodynamic forces applied at the apical surface of vascular endothelial cells (ECs) provide the mechanical signals at intracellular organelles and through the inter-connected cellular network. The objective of this study is to quantify the intracellular and intercellular stresses in a confluent vascular EC monolayer. A novel three-dimensional, multiscale and multicomponent model of focally adhered ECs is developed to account for the role of potential mechanosensors (glycocalyx layer, actin cortical layer, nucleus, cytoskeleton, focal adhesions (FAs) and adherens junctions (ADJs)) in mechanotransmission and EC deformation. The overriding issue addressed is the stress amplification in these regions, which may play a role in subcellular localization of mechanotransmission. The model predicts that the stresses are amplified 250-600-fold over apical values at ADJs and 175-200-fold at FAs for ECs exposed to a mean shear stress of 10 dyne cm 22 . Estimates of forces per molecule in the cell attachment points to the external cellular matrix and cell-cell adhesion points are of the order of 8 pN at FAs and as high as 3 pN at ADJs, suggesting that direct force-induced mechanotransmission by single molecules is possible in both. The maximum deformation of an EC in the monolayer is calculated as 400 nm in response to a mean shear stress of 1 Pa applied over the EC surface which is in accord with measurements. The model also predicts that the magnitude of the cell-cell junction inclination angle is independent of the cytoskeleton and glycocalyx. The inclination angle of the cell-cell junction is calculated to be 6.68 in an EC monolayer, which is somewhat below the measured value (9.98) reported previously for ECs subjected to 1.6 Pa shear stress for 30 min. The present model is able, for the first time, to cross the boundaries between different length scales in order to provide a global view of potential locations of mechanotransmission.

Pulsatile blood flow is studied in a three-dimensional model of human thoracic aorta at different stages of atherosclerotic lesion growth, taking into account the effect of atherosclerotic plaque location and peripheral symmetry. The model is reconstructed from the computed tomography images. The wall shear stress (WSS), time-averaged WSS, and the oscillatory shear index are applied to determine susceptible sites for the onset of early atherosclerosis. Then, two different degrees of stenosis severity, 50 and 80 %, are introduced to vulnerable areas of the healthy aorta geometry. The overriding issue addressed is that the WSS distribution and magnitude are strongly affected by the atherosclerotic plaque size, its symmetric features, and the location, i.e., the branch it is formed. The present study, for the first time, is capable of providing information on the high shear environment that may exist upon the rupture of plaque surface and any thrombosis due to platelet deposition. The magnitude of WSS and its distribution at the throat of 50 % stenosed aortic arch are in agreement with the previous numerical study (Huang et al. in Exp Fluids 48(3):497-508, 2010). Results show that WSS values exceed 50 Pa at the throat of 80 % stenosed left common carotid and brachiocephalic arteries.

Segmented polyurethane (PU) has proven to be the best biomaterial for artificial heart valves, but the calcification of polyurethane surfaces causes serious problems in long-term implants. This work was undertaken to evaluate the effects of polydimethylsiloxane (PDMS) grafting on the calcification, biocompatibility, and blood compatibility of polyurethane. A grafted polyurethane film was compared with virgin polyurethane surfaces. Physical properties of the samples were examined using different techniques. The hydrophobicity of the polyurethane films increased as a result of silicone modification. The effects of surface modification of polyurethane films on their calcification and fibroblast cell (L 929) and platelet behavior were evaluated in vitro. Fourier transform infrared spectroscopy indicated the direct involvement of the polyether soft segments of the polymer in the calcification process. Scanning electron microscopy of films indicated that grafting of silicone rubber to the surface of polyurethane successfully prevented the calcification process. The morphology of fibroblast cells that adhered to the PU films and modified films was similar to that of controls and showed the same proliferation. On the other hand, grafting PDMS onto PU did not affect the amount of platelets that adhered to the polyurethane surfaces.

Introduction-The adhesion of tumor cells to vessel wall is a critical stage in cancer metastasis. Firm adhesion of cancer cells is usually followed by their extravasation through the endothelium. Despite previous studies identifying the influential parameters in the adhesive behavior of the cancer cell to a planer substrate, less is known about the interactions between the cancer cell and microvasculature wall and whether these interactions exhibit organ specificity. The objective of our study is to characterize sizes of microvasculature where a deformable circulating cell (DCC) would firmly adhere or roll over the wall, as well as to identify parameters that facilitate such firm adherence and underlying mechanisms driving adhesive interactions. Methods-A three-dimensional model of DCCs is applied to simulate the fluid-structure interaction between the DCC and surrounding fluid. A dynamic adhesion model, where an adhesion molecule is modeled as a spring, is employed to represent the stochastic receptor-ligand interactions using kinetic rate expressions. Results-Our results reveal that both the cell deformability and low shear rate of flow promote the firm adhesion of DCC in small vessels (<10 lm). Our findings suggest that ligandreceptor bonds of PSGL-1-P-selectin may lead to firm adherence of DCC in smaller vessels and rolling-adhesion of DCC in larger ones where cell velocity drops to facilitate the activation of integrin-ICAM-1 bonds. Conclusions-Our study provides a framework to predict accurately where different DCC-types are likely to adhere firmly in microvasculature and to establish the criteria predisposing cancer cells to such firm adhesion.