Biorheology - Volume 52, issue 5-6

Authors: Lipowsky, Herbert H. | Nash, Gerard

Article Type: Editorial

DOI: 10.3233/BIR-150674

Citation: Biorheology, vol. 52, no. 5-6, pp. 293-294, 2015

Authors: Chien, Shu

Article Type: Other

DOI: 10.3233/BIR-150675

Citation: Biorheology, vol. 52, no. 5-6, pp. 295-299, 2015

Authors: Cokelet, Giles R.

Article Type: Other

DOI: 10.3233/BIR-150676

Citation: Biorheology, vol. 52, no. 5-6, pp. 301-302, 2015

Authors: Zhu, Shu | Herbig, Bradley A. | Li, Ruizhi | Colace, Thomas V. | Muthard, Ryan W. | Neeves, Keith B. | Diamond, Scott L.

Article Type: Review Article

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. Show more

Keywords: Harry Goldsmith, microfluidics, hemorheology, platelet, von Willebrand factor

DOI: 10.3233/BIR-15065

Citation: Biorheology, vol. 52, no. 5-6, pp. 303-318, 2015

Authors: Gogia, Shobhit | Neelamegham, Sriram

Article Type: Review Article

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. Show more

Keywords: Hydrodynamic force, thrombosis, blood, rheology, von Willebrand factor, ADAMTS-13, platelet, flow chamber

DOI: 10.3233/BIR-15061

Citation: Biorheology, vol. 52, no. 5-6, pp. 319-335, 2015

Authors: Mazor, Rafi | Schmid-Schönbein, Geert W.

Article Type: Review Article

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. Show more

Keywords: Matrix metalloproteinase, serine protease, pancreatic digestive enzyme, cell rheology, mechanotransduction, hypertension, insulin resistance, rarefaction, autodigestion, spontaneously hypertensive rat

DOI: 10.3233/BIR-15045

Citation: Biorheology, vol. 52, no. 5-6, pp. 337-352, 2015

Authors: Fan, Zhichao | Ley, Klaus

Article Type: Review Article

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.

Keywords: Talin, RIAM, kindlin-3, PSGL-1, GPCR, Rap-1

DOI: 10.3233/BIR-15085

Citation: Biorheology, vol. 52, no. 5-6, pp. 353-377, 2015

Authors: Zhengwen, Zhang | Meiselman, Herbert J. | Neu, Björn

Article Type: Research Article

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. Show more

Keywords: Adhesion, depletion interaction, dextran, red blood cell, interference reflection microscopy

DOI: 10.3233/BIR-15044

Citation: Biorheology, vol. 52, no. 5-6, pp. 379-389, 2015

Authors: Watts, Tim | Barigou, Mostafa | Nash, Gerard B.

Article Type: Research Article

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. Show more

Keywords: Leukocyte adhesion, platelet adhesion, margination

DOI: 10.3233/BIR-15043

Citation: Biorheology, vol. 52, no. 5-6, pp. 391-404, 2015

Authors: Herant, Marc | Dembo, Micah

Article Type: Research Article

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. Show more

Keywords: Cell motility, cell mechanics, lamella, cytoskeleton, membrane tension, membrane curvature

DOI: 10.3233/BIR-14042

Citation: Biorheology, vol. 52, no. 5-6, pp. 405-414, 2015