Flow across microvessel walls through the endothelial surface glycocalyx and the interendothelial cleft

Sugihara‐Seki, Masako; Akinaga, Takeshi; Itano, Tomoaki

doi:10.1017/s0022112008000530

Cited by 19 publications

(19 citation statements)

References 57 publications

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“…The major molecular components of the glycocalyx are proteoglycans with their glycosaminoglycan side chains and glycoproteins (24). However, resent observations from autocorrelation imaging techniques have suggested a structural model for the glycocalyx, which is composed of bush-like clusters of core proteins (22,32). Based on these images, we model the glycocalyx as a fiber matrix characterized by a (Darcy) hydraulic permeability coefficient, K Pg, given by (32): (10) where af is the fiber radius (6 nm) and ⌬ is the spacing between fibers (20 nm).…”

Section: Methodsmentioning

confidence: 99%

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The transport of LDL across the deformable arterial wall: the effect of endothelial cell turnover and intimal deformation under hypertension

Dabagh

Jalali²,

Tarbell³

2009

American Journal of Physiology-Heart and Circulatory Physiology

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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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Section: Methodsmentioning

confidence: 99%

“…The tight junctions form lines of contact between the adjacent cells and act as barrier for water and solute to flow within the cleft (22). The dominant pathway for water through tight junctions in clefts is large, infrequent, widely spaced breaks (22,32).…”

Section: Methodsmentioning

confidence: 99%

The transport of LDL across the deformable arterial wall: the effect of endothelial cell turnover and intimal deformation under hypertension

Dabagh

Jalali²,

Tarbell³

2009

American Journal of Physiology-Heart and Circulatory Physiology

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“…Note that the interfinger distance is 1 mm and the density of ADJs is 1 mm 22 [59 -61]. ADJs are located at 25% of the cleft depth or 250 nm from the apical surface [36,73]. The shape, location and distribution of ADJs in the cell -cell interface in this model are shown in figure 1d.…”

Section: Geometric Modelmentioning

confidence: 99%

“…The glycocalyx layer has been described as a mechanosensor and transducer of FSS on ECs [1,5,[25][26][27][28][29][30][31][32][33][34][35][36]. Theoretical models to describe the transmission of force from fluid flow to the surface of cells covered by glycocalyx have revealed & 2014 The Author(s) Published by the Royal Society.…”

Section: Introductionmentioning

confidence: 99%

Shear-induced force transmission in a multicomponent, multicell model of the endothelium

Dabagh

Jalali

Butler

et al. 2014

J. R. Soc. Interface.

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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.

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“…Most existing models of transport through the inter-endothelial clefts are based on continuum approaches. However, it was suggested that more suitable analyses should be based on the molecular nature of the fluid because of the sizes of the mean intermolecular distances (∼ 0.3 nm) and the cleft width (∼18 nm) (Sugihara-Seki et al 2008). The development of multiscale computational models (Praprotnik and Delle Site 2008), coupling, for example, the molecular structure of the glycocalyx with a continuum description of the flow, is highly suitable in this context.…”

Section: Models Of Vascular Transport and Angiogenesismentioning

confidence: 99%

The Impact of Computational Fluid Mechanics on Cancer Research

Belisario

Sigalotti

2014

Computational and Experimental Fluid Mechanics With Applications to Physics, Engineering and the Environment

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This chapter presents an overview of recent contributions that show how fluid mechanics is drastically changing cancer research. The review will mainly focus on the computational modelling of fluid-mediated processes related to cancer dynamics, spanning different representation scales from cells to organs. Fluid mechanics seems to act as a fundamental organizing principle in many aspects of cancer, including its growth, progression, metastasis, and therapy. On the other hand, it is clear that fluid-dynamics modelling can make a huge contribution to many areas of experimental cancer investigation since there is now a wealth of data that requires systematic analysis. The relevance of microfluidics in the isolation, detection, molecular characterization, and migration of tumour cells is also discussed. In the last part of the chapter, future challenges and perspectives are briefly outlined.

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Flow across microvessel walls through the endothelial surface glycocalyx and the interendothelial cleft

Cited by 19 publications

References 57 publications

The transport of LDL across the deformable arterial wall: the effect of endothelial cell turnover and intimal deformation under hypertension

The transport of LDL across the deformable arterial wall: the effect of endothelial cell turnover and intimal deformation under hypertension

Shear-induced force transmission in a multicomponent, multicell model of the endothelium

The Impact of Computational Fluid Mechanics on Cancer Research

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