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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: Microfluidic devices create precisely controlled reactive blood flows and typically involve: (i) validated anticoagulation/pharmacology protocols, (ii) defined reactive surfaces, (iii) defined flow-transport regimes, and (iv) optical imaging. An 8-channel device can be run at constant flow rate or constant pressure drop for blood perfusion over a patterned collagen, collagen/kaolin, or collagen/tissue factor (TF) to measure platelet, thrombin, and fibrin dynamics during clot growth. A membrane-flow device delivers a constant flux of platelet agonists or coagulation enzymes into flowing blood. A trifurcated device sheaths a central blood flow on both sides with buffer, an ideal approach for on-chip recalcification…of citrated blood or drug delivery. A side-view device allows clotting on a porous collagen/TF plug at constant pressure differential across the developing clot. The core-shell architecture of clots made in mouse models can be replicated in this device using human blood. For pathological flows, a stenosis device achieves shear rates of >100,000 s−1 to drive plasma von Willebrand factor (VWF) to form thick long fibers on collagen. Similarly, a micropost-impingement device creates extreme elongational and shear flows for VWF fiber formation without collagen. Overall, microfluidics are ideal for studies of clotting, bleeding, fibrin polymerization/fibrinolysis, cell/clot mechanics, adhesion, mechanobiology, and reaction-transport dynamics.
Keywords: Harry Goldsmith, microfluidics, hemorheology, platelet, von Willebrand factor
vol. 52, no. 5-6, pp. 303-318, 2015
Abstract: Von Willebrand factor (VWF) is the largest glycoprotein in blood. It plays a crucial role in primary hemostasis via its binding interaction with platelet and endothelial cell surface receptors, other blood proteins and extra-cellular matrix components. This protein is found as a series of repeat units that are disulfide bonded to form multimeric structures. Once in blood, the protein multimer distribution is dynamically regulated by fluid shear stress which has two opposing effects: it promotes the aggregation or self-association of multiple VWF units, and it simultaneously reduces multimer size by facilitating the force-dependent cleavage of the protein by various proteases,…most notably ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type repeats, motif 1 type 13). In addition to these effects, fluid shear also controls the solution and substrate-immobilized structure of VWF, the nature of contact between blood platelets and substrates, and the biomechanics of the GpIbα –VWF bond. These features together regulate different physiological and pathological processes including normal hemostasis, arterial and venous thrombosis, von Willebrand disease, thrombotic thrombocytopenic purpura and acquired von Willebrand syndrome. This article discusses current knowledge of VWF structure–function relationships with emphasis on the effects of hydrodynamic shear, including rapid methods to estimate the nature and magnitude of these forces in selected conditions. It shows that observations made by many investigators using solution and substrate-based shearing devices can be reconciled upon considering the physical size of VWF and the applied mechanical force in these different geometries.
Abstract: Abnormal blood rheological properties seldom occur in isolation and instead are accompanied by other complications, often designated as co-morbidities. In the metabolic syndrome with complications like hypertension, diabetes and lack of normal microvascular blood flow, the underlying molecular mechanisms that simultaneously lead to elevated blood pressure and diabetes as well as abnormal microvascular rheology and other cell dysfunctions have remained largely unknown. In this review, we propose a new hypothesis for the origin of abnormal cell functions as well as multiple co-morbidities. Utilizing experimental models for the metabolic disease with diverse co-morbidities we summarize evidence for the presence of an…uncontrolled extracellular proteolytic activity that causes ectodomain receptor cleavage and loss of their associated cell function. We summarize evidence for unchecked degrading proteinase activity, e.g. due to matrix metalloproteases, in patients with hypertension, Type II diabetes and obesity, in addition to evidence for receptor cleavage in the form of receptor fragments and decreased extracellular membrane expression levels. The evidence suggest that a shift in blood rheological properties and other co-morbidities may in fact be derived from a common mechanism that is due to uncontrolled proteolytic activity, i.e. an early form of autodigestion. Identification of the particular proteases involved and the mechanisms of their activation may open the door to treatment that simultaneously targets multiple co-morbidities in the metabolic syndrome.
Abstract: Integrins are a group of heterodimeric transmembrane receptors that play essential roles in cell–cell and cell–matrix interaction. Integrins are important in many physiological processes and diseases. Integrins acquire affinity to their ligand by undergoing molecular conformational changes called activation. Here we review the molecular biomechanics during conformational changes of integrins, integrin functions in leukocyte biorheology (adhesive functions during rolling and arrest) and molecules involved in integrin activation.
Abstract: Background: Cell–cell and cell–surface adhesion modulated by water-soluble polymers continues to be of current interest, especially since prior reports have indicated a role for depletion-mediated attractive forces. Objective: To determine the effects of concentration and molecular mass of the neutral polymer dextran (40 kDa to 28 MDa) on the adhesion of human red blood cells (RBC) to coated glass coverslips. Methods: Confocal-reflection interference contrast microscopy (C-IRM), in conjunction with phase contrast imaging, was utilized to measure the adhesion dynamics and contact mechanics of RBC during the initial stages of cell contact with several types of substrates.…Results: Adhesion is markedly increased in the presence of dextran with a molecular mass ⩾ 70 kDa. This increased adhesiveness is attributed to reduced surface concentration of the large polymers and hence increased attractive forces due to depletion interaction. The equilibrium deformation of adhering RBC was modeled as a truncated sphere and the calculated adhesion energies were in close agreement with theoretical results. Conclusions: These results clearly demonstrate that polymer depletion can promote RBC adhesion to artificial surfaces and suggest that this phenomenon may play a role in other specific and non-specific cell–cell interactions, such as rouleau formation and RBC–endothelial cell adhesion.
Abstract: Background: Leukocytes and platelets typically fulfil their functions through adhesion to the walls of vessels with different size, haematocrit and shear rate. Objective: We aimed to investigate differential effects of these variables on leukocyte and platelet adhesion. Methods: Blood with varying haematocrit was perfused at a range of wall shear rates through capillaries of depth 100 or 300 µm coated with P-selectin or collagen. Results: Adhesion of leukocytes was much more efficient in the smaller capillaries, but was equal on the upper and lower surfaces and showed nearly identical shear rate dependence for either size…of vessel. Platelets also adhered more efficiently in the smaller vessels (although the effect of size was not so great), and equally on upper and lower surfaces, but their adhesion was much less sensitive to increasing shear rate. In previous studies using vertically-orientated capillaries, leukocyte adhesion increased with increasing haematocrit (Am. J. Physiol. 285 (2003), H229–H240). Here, in horizontal 100 µm capillaries, leukocyte adhesion was highly efficient at haematocrit of 10% but restricted to the lower surface. Adhesion decreased initially as haematocrit was increased to 30% and then increased slightly again at 40% haematocrit. Increasing haematocrit supported a monotonic increase in platelet adhesion in the horizontal capillaries. Conclusions: Platelets adhere efficiently over a wider range of sizes and shear rates, and at high haematocrit. Leukocytes adhere better in smaller vessels and at low haematocrit in horizontal vessels. The different behaviours may represent ‘rheological adaptation’ to functions in inflammation vs. haemostasis.
Abstract: Background: The processes of cell spreading and crawling are frequently associated with mysterious waves and ruffling cycles of the leading edge. Objective: To develop a physical model that can account for these phenomena based on a few simple and plausible rules governing adhesion, contractility, polymerization of cytoskeleton, and membrane tension. Methods: Extension of a continuum mechanical model of phagocytosis [J Cell Sci. (2006);119(Pt 9):1903–13] adding a simple coupling between membrane curvature and cytoskeletal polymerization. Results: We show that our generalized model has just the right nonlinearity needed for triggering of stochastic/chaotic cycles of ruffling…similar to those that are observed in real cells. Conclusions: The cycles are caused by a branching instability at the leading edge that leads to bifurcations of protrusion into forward moving lamellipodium and upward and rearward folding ruffles. The amplitude of the instability is modulated by the surface tension, with higher tension stabilizing against ruffling (but inhibiting protrusion) and lower tension promoting ruffling and protrusion.
Abstract: Background: During inflammation leukocyte attachment to the blood vessel wall is augmented by capture of near-wall flowing leukocytes by previously adherent leukocytes. Adhesive interactions between flowing and adherent leukocytes are mediated by L-selectin and P-selectin Glycoprotein Ligand-1 (PSGL-1) co-expressed on the leukocyte surface and ultimately regulated by hydrodynamic shear thresholding. Objective: We hypothesized that leukocyte deformability is a significant contributory factor in shear thresholding and secondary capture. Methods: Cytochalasin D (CD) was used to increase neutrophil deformability and fixation was used to reduce deformability. Neutrophil rolling on PSGL-1 coated planar surfaces and collisions with PSGL-1 coated…microbeads were analyzed using high-speed videomicroscopy (250 fps). Results: Increased deformability led to an increase in neutrophil rolling flux on PSGL-1 surfaces while fixation led to a decrease in rolling flux. Abrupt drops in flow below the shear threshold resulted in extended release times from the substrate for CD-treated neutrophils, suggesting increased bond number. In a cell-microbead collision assay lower flow rates were correlated with briefer adhesion lifetimes and smaller adhesive contact patches. Conclusions: Leukocyte deformation may control selectin bond number at the flow rates associated with hydrodynamic shear thresholding. Model analysis supported a requirement for both L-selectin catch-slip bond properties and multiple bond formation for shear thresholding.
Abstract: Background: The endothelial glycocalyx serves as a barrier to leukocyte (WBC)-endothelium (EC) adhesion. Shedding of glycans, by matrix metalloproteases (MMPs) exposes EC integrin receptors to facilitate firm adhesion. However, the effect of shedding on the strength of the adhesive bond remains to be determined. Objectives: Examine the effect of MMP inhibition on the kinetics of WBC-EC adhesion under normal and inflammatory conditions to delineate differences in the duration and number of adhesive bonds. Methods: WBC adhesion in post-capillary venules was observed in rat mesentery. Adhesion duration and off-rates (K OFF )…were correlated with shear stress during adhesion in response to 1 µM fMLP or 0.5 µM doxycycline (doxy, to inhibit MMP activation). Results: Doxy increased mean adhesion time significantly from 2.5 (control) to 5.6 s, whereas fMLP increased it 8-fold to 20 s, which was not affected by pre-treatment with doxy. Estimates of the number of adhesive bonds (simplified Bell-model) revealed a significantly greater increase with fMLP compared to doxy alone, with no effect on fMLP by pretreatment with doxy. With doxy alone, K OFF was significantly 4-fold greater compared to fMLP, suggesting a much weaker bond. Conclusions: Although the increased number of bonds by MMP inhibition with doxy alone and fMLP were similar, the bonds due to doxy appeared weaker as evidenced by their shorter duration, and lesser reduction in K OFF relative to control. Thus doxy limits the availability of integrin binding sites during fMLP stimulated adhesion, but has a pro-adhesive effect due to increased ligands for WBC binding that arises from inhibition of normal sheddase activity on the EC.
Keywords: Leukocyte adhesion, matrix metalloproteases, MMPs, adhesion duration, bond force
vol. 52, no. 5-6, pp. 433-445, 2015
Abstract: Background: Recombinant atrial natriuretic peptide (ANP) is administered in patients with acute heart failure in Japan to improve renal function and hemodynamics, but its anti-inflammatory effect on activated leukocytes may also contribute to its therapeutic efficacy. Objective: Examine unconventional role of ANP in neutrophil adhesion to inflamed endothelium. Methods: Human neutrophils were perfused over endothelial monolayers in a microfluidic lab-chip assay. Cell rheology was assessed by micropipette aspiration to assess changes in cortical tension and viscosity. Fluorescence microscopy was applied to measure adhesive contact area and β 2 -integrin focal bond…formation. Results: ANP inhibited neutrophil rolling and firm adhesion without influencing the upregulation of cellular adhesion molecules on endothelium or the regulation of high affinity CD18 and shedding of L-selectin during neutrophil activation. Exposed to fluid shear, integrin mediated arrest was disrupted with ANP treatment, which elicited formation of long tethers and diminished cell spreading and contact. This correlated with a ∼40% increase in neutrophil viscosity and a reduction in the adhesive footprint. Conclusions: A decrease in cell deformation and neutrophil flattening with ANP results in fewer integrin bond clusters, which translates to higher tensile forces and impaired adhesion strengthening and cell detachment.