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Biorheology is an international interdisciplinary journal that publishes research on the deformation and flow properties of biological systems or materials. It is the aim of the editors and publishers of
Biorheology to bring together contributions from those working in various fields of biorheological research from all over the world. A diverse editorial board with broad international representation provides guidance and expertise in wide-ranging applications of rheological methods to biological systems and materials.
The aim of biorheological research is to determine and characterize the dynamics of physiological processes at all levels of organization. Manuscripts should report original theoretical and/or experimental research promoting the scientific and technological advances in a broad field that ranges from the rheology of macromolecules and macromolecular arrays to cell, tissue and organ rheology. In all these areas, the interrelationships of rheological properties of the systems or materials investigated and their structural and functional aspects are stressed.
The scope of papers solicited by
Biorheology extends to systems at different levels of organization that have never been studied before, or, if studied previously, have either never been analyzed in terms of their rheological properties or have not been studied from the point of view of the rheological matching between their structural and functional properties. This biorheological approach applies in particular to molecular studies where changes of physical properties and conformation are investigated without reference to how the process actually takes place, how the forces generated are matched to the properties of the structures and environment concerned, proper time scales, or what structures or strength of structures are required.
Biorheology invites papers in which such 'molecular biorheological' aspects, whether in animal or plant systems, are examined and discussed. While we emphasize the biorheology of physiological function in organs and systems, the biorheology of disease is of equal interest. Biorheological analyses of pathological processes and their clinical implications are encouraged, including basic clinical research on hemodynamics and hemorheology.
In keeping with the rapidly developing fields of mechanobiology and regenerative medicine,
Biorheology aims to include studies of the rheological aspects of these fields by focusing on the dynamics of mechanical stress formation and the response of biological materials at the molecular and cellular level resulting from fluid-solid interactions. With increasing focus on new applications of nanotechnology to biological systems, rheological studies of the behavior of biological materials in therapeutic or diagnostic medical devices operating at the micro and nano scales are most welcome.
Abstract: BACKGROUND: Atherosclerotic lesions develop preferentially at certain sites in the human arterial system, such as the inner wall of curved segments and the outer wall of bifurcations. Local wall shear stress (WSS) and concentration of low density lipoprotein (LDL) have been identified as two important factors contributing to these lesions. OBJECTIVE: To determine if a connection exists between arterial curvature and the formation of atherosclerosis. METHODS: A set of 3-D vessel models with different bend angles was constructed. By comparing blood flow, WSS, and LDL aggregation, the influence of bend curvature on atherosclerotic lesions was assessed.…RESULTS: Upon increasing arterial bending, low WSS regions were formed at the outer wall of the junction between straight and curved segments, as well as the inner wall of curved segments. However, high LDL concentrations only appeared at the inner wall of the bend region. A connection between secondary flow and LDL concentration was observed; high LDL concentration regions had stronger secondary flow. Higher water infiltration velocity could enhance LDL aggregation, while blood non-Newtonian properties, by easing secondary flow, diminished its aggregation. CONCLUSIONS: Under the same flow rate, a larger bend angle increased flow resistance, lowered WSS, and increased LDL surface concentrations, thus indicating an increased risk of atherosclerosis.
Keywords: Bend angle, wall shear stress, concentration polarization, secondary flow
vol. Pre-press, no. Pre-press, pp. 1-11, 2019
Abstract: BACKGROUND: Previous studies have demonstrated that the glycosaminoglycans (GAGs) heparan sulfate (HS) and hyaluronic acid (HA) are mechanosensors for interstitial flow on cancer cells. The proteins that link the GAGs to the cancer cell for mechanotransduction, however, are not known. OBJECTIVE: To assess whether the HS proteoglycan core proteins, glypican-1 and syndecan-1, or the HA receptor, CD44, provides the mechanical linkage to the cell. METHODS: The highly metastatic renal carcinoma cell line (SN12L1) and its companion low metastatic cell line (SN12C) were analyzed by Western blot, siRNA, and a 3-dimensional interstitial flow migration assay.…RESULTS: There was significant elevation of glypican-1 protein expression in the SN12L1 cells relative to the SN12C cells while there were no significant differences in syndecan-1 or CD44. Knock down of glypican-1 by siRNA completely blocked flow induced migration in SN12L1 cells. MAPK inhibitors also blocked flow induced migration in SN12L1 cells. CONCLUSIONS: Glypican-1 provides the mechanical linkage from HS (the flow sensor) to the SN12L1 cell where mechanotransduction leading to the enhancement of migration (metastasis) occurs. MAPKs downstream of Glypican-1 propagate the signal. The HS, Glypican-1, MAPK signaling axis suggests opportunities for pharmaceutical intervention.
Abstract: The endothelial glycocalyx (eGlx) constitutes the first barrier to protein in all blood vessels. This is particularly noteworthy in the renal glomerulus, an ultrafiltration barrier. Leakage of protein, such as albumin, across glomerular capillaries results in albumin in the urine (albuminuria). This is a hall mark of kidney disease and can reflect loss of blood vessel integrity in microvascular beds elsewhere. We discuss evidence demonstrating that targeted damage to the glomerular eGlx results in increased glomerular albumin permeability. EGlx is lost in diabetes and experimental models demonstrate loss from glomerular endothelial cells. Vascular endothelial growth factor (VEGF)A is upregulated in…early diabetes, which is associated with albuminuria. Treatment with paracrine growth factors such as VEGFC, VEGF165 b and angiopoietin-1 can modify VEGFA signalling, rescue albumin permeability and restore glomerular eGlx in models of diabetes. Manipulation of VEGF receptor 2 signalling, or a common eGlx biosynthesis pathway by these growth factors, may protect and restore the eGlx layer. This would help to direct future therapeutics in diabetic nephropathy.
vol. Pre-press, no. Pre-press, pp. 1-17, 2019
Abstract: BACKGROUND: In order to play different roles in vascular functions as a mechanosensor to blood flows and as a barrier to transvascular exchange, the endothelial surface glycocalyx (ESG) should have an organized structure. Due to the limitations of optical and electron microscopy, the ultra-structure of ESG has not been revealed until the recent development of super-resolution optical microscopy, STORM. OBJECTIVES: To investigate the ESG components and their organization on bEnd3 (mouse brain microvascular endothelial cells) monolayer. METHODS: ESG was immunolabeled with anti-heparan sulfate (HS), followed by an ATTO488 conjugated goat anti-mouse IgG, and with biotinylated hyaluronic…acid (HA) binding protein, followed by an AF647 conjugated anti-biotin. The ESG was then imaged by the STORM. RESULTS: HA is a long molecule weaving into a network which covers the endothelial luminal surface. In contrast, HS is a shorter molecule, perpendicular to the cell surface. HA and HS are partially overlapped with each other at the endothelial luminal surface. We also quantified the length, diameter, orientation, and density of HS at the top, middle and bottom regions of the endothelial surface. CONCLUSIONS: Our results suggest that HS plays a major role in mechanosensing and HA plays a major role in the molecular sieve.
Abstract: Diabetic retinopathy is known as a microvascular complication of hyperglycemia, with a breakdown of the blood-retinal barrier, loss of pericytes, formation of microhemorrhages, early decreases in perfusion and areas of ischemia, with the latter speculated to induce the eventual proliferative, angiogenic phase of the disease. Our animal models of diabetic retinopathy demonstrate similar decreases in retinal blood flow as seen in the early stages of diabetes in humans. Our studies also show an alteration in the retinal distribution of red blood cells, with the deep capillary layer receiving a reduced fraction, and with flow being diverted more towards the superficial…vascular layer. Normal red blood cell distribution is dependent on the presence of the endothelial surface layer, specifically the glycocalyx, which has been reported to be partially lost in the diabetic retina of both humans and animals. This review addresses these two phenomena in diabetes: altered perfusion patterns and loss of the glycocalyx, with a possible connection between the two.
Abstract: BACKGROUND: The onset of many disease processes depends on the function of the endothelial cell (EC) glycocalyx (GCX) which acts as a flow-dependent barrier to cellular infiltration and molecular transport across the blood vessel wall. OBJECTIVE: This review aims to examine these processes with the potential end goal of implementing GCX repair to restore EC barrier function and slow the progression of disease. METHODS: Cell and mouse studies were employed to examine the state of EC GCX in healthy versus disruptive flow conditions. Correlates of observations of the GCX with a number of EC functions were…sought with an emphasis on studies of trans-endothelial barrier integrity against vessel wall infiltration of cells and molecules from the circulation. To demonstrate the importance of GCX as a regulator of trans-endothelial infiltration, assays were performed using ECs with an intact GCX and compared to assays of ECs with an experimentally degraded GCX. Studies were also conducted of ECs in which a degraded GCX was repaired. RESULTS: In healthy flow conditions, the EC GCX was found to be thick and substantially covered the endothelial surface. GCX expression dropped significantly in complex flow conditions and coincided with a disease-like cellular and molecular accumulation in the endothelium or within the blood vessel wall. Therapeutic repair of the GCX abolished this accumulation. CONCLUSIONS: Regenerating the degraded GCX reverses EC barrier dysfunction and may attenuate the progression of vascular disease.
Abstract: BACKGROUND: Ultrastructural investigations of the endothelial glycocalyx reveal a layer adjacent to the cell surface with a structure consistent with the primary ultrafilter of vascular walls. Theory predicts this layer can be no greater than 200–300 nm thick, a result to be reconciled with observations that red cells and large macromolecules are excluded from a region 1 micrometer or more from the cell membrane. OBJECTIVE: To determine whether this apparent inconsistency might be accounted for by a model of steady state water and protein transport through a glycocalyx bi-layer formed by a porous outer layer in series with a more selective inner layer.…METHODS: Expressions for coupled water and albumin fluxes through the two layers were used to describe steady state ultra-filtration though the bi-layer model. RESULTS: Albumin accumulates at the interface between the porous layer and the selective inner layer. The osmotic pressure of accumulated albumin significantly modifies the observed permeability properties of the microvessel wall by an effective unstirred layer effect. CONCLUSIONS: The model places significant constraints on the outer layer permeability properties . The only outer layer properties that are consistent with measured steady state filtration rates and models of red cell flux through microvessels are an albumin permeability coefficient and hydraulic conductivity more than an order of magnitude larger than the those of the inner layer.
Abstract: BACKGROUND: The endothelial glycocalyx plays a pivotal role in regulating blood flow, filtering blood components, sensing and transducing mechanical signals. These functions are intimately related to its dynamics at the molecular level. OBJECTIVE: The objective of this research is to establish the relationship between the functions of the endothelial glycocalyx and its dynamics at the molecular level. METHODS: To establish such a relationship, large-scale molecular dynamics simulations were undertaken to mimic the dynamics of the glycocalyx and its components in the presence of flow shear stresses. RESULTS: First, motions of the glycocalyx core protein…and the pertinent subdomains were scrutinised. Three-directional movements of the glycocalyx core protein were observed, although the flow was imposed only in the x direction. Such an observation contributes to understanding the glycocalyx redistribution as reported in experiments. Unsynchronised motion of the core protein subdomains was also spotted, which provides an alternative explanation of macroscopic phenomena. Moreover, the dynamics, root-mean-square-deviations and conformational changes of the sugar chains were investigated. Based on the findings, an alternative force transmission pathway, the role of sugar chains, and potential influence on signalling transduction pathway were proposed and discussed. CONCLUSIONS: This study relates the functions of the glycocalyx with its microscopic dynamics, which fills a knowledge gap about the links between different scales.