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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: The interaction between granulocytes and endothelial walls may be influenced by the blood flow. This possibility was investigated by studying the influence of fluid flow on the adhesion and detachment of 51 Cr-labeled rat granulocytes interacting with protein-coated glass surfaces. It is concluded that: i) Adhesion is markedly decreased when the wall shear rate becomes higher than about 20 s−1 . ii) Pretreating glass with concanavalin A or polylysine significantly decreased adhesion, whereas fibronectin had little effect on binding. iii) Very high flow rates (about one thousandfold higher than those compatible with bond formation) were required to provoke…substantial detachment of substrate-bound cells. iv) Coating glass with laminin or polylysine decreased binding strength whereas fibronectin or concanavalin A did not substantially influence this parameter. v) Exposing granulocytes to phorbol myristate acetate might increase the cell ability to form strong adhesions, whereas labile adhesion was unaffected or even decreased by this treatment. Adhesion is markedly decreased when the wall shear rate becomes higher than about 20 s−1 . Pretreating glass with concanavalin A or polylysine significantly decreased adhesion, whereas fibronectin had little effect on binding. Very high flow rates (about one thousandfold higher than those compatible with bond formation) were required to provoke substantial detachment of substrate-bound cells. Coating glass with laminin or polylysine decreased binding strength whereas fibronectin or concanavalin A did not substantially influence this parameter. Exposing granulocytes to phorbol myristate acetate might increase the cell ability to form strong adhesions, whereas labile adhesion was unaffected or even decreased by this treatment.
Keywords: Adhesion, Granulocyte, Flow
vol. 27, no. 3-4, pp. 433-444, 1990
Abstract: Pentoxifylline (PTX) has been reported to enhance the early accumulation of neutrophils at the site of Staphylococcus aureus subcutaneous infection in mice (1) and to stimulate in vitro PMN chemotaxis, particularly under dense agarose (2). Among the biochemical events contributing to chemotaxis are actin polymerization (3). The membrane cytoskeleton is believed to control the lateral mobility of integral membrane proteins as well as influencing cell shape and mobility. Thus, pharmacological modulations of neutrophil chemotaxis may be related to an effect of the pharmacological agents on the membrane cytoskeleton. The present study was designed to characterize the effect of PTX…on actin polymerization of freely-suspended PMN before and after stimulation by the chemotactic factor f-MLP. We used flow cytometry to determine the proportion of actin in the filamentous form, and Rhodamine-Phalloidin as fluorescent probe (4). PTX decreased actin polymerization in response to stimulation by f-MLP. The reduction in F-actin by PTX was higher in the samples with higher activation ratios as compared with untreated PMN.
Abstract: Polymorphonuclear (PMN) overactivation plays a critical role in microcirculation as well as in conditions such as multiorgan failure (MOF). Pentoxifylline has been shown to prevent PMN activation by endotoxin and cytokines such as TNFalpha and IL-1. In addition, MOF induced by IL-2 in animals can be prevented by pentoxifylline. The present studies evaluated two aspects of PMN activation and pentoxifylline interaction. The first was the time sequence for pentoxifylline prevention of TNFalpha activation and the second was the activity of pentoxifylline on amphotericin B activation of PMNs. TNFalpha activation of PMNs is blocked by pentoxifylline when cells…are exposed to pentoxifylline prior to TNFalpha or after TNFalpha . Amphotericin B activation of PMNs was demonstrated by a decreased chemotaxis, increased chemiluminescence, and increased PMN spreading. In all conditions, pentoxifylline decreased amphotericin B activation of PMNs. These results suggest that pentoxifylline can reverse cytokine activation of PMNs and that pentoxifylline may alter some of the toxic effects of amphotericin.
Abstract: Endothelial cells play an important role in the regulation of thrombosis. Normal resting (i.e. unstimulated) endothelial cells exhibit antithrombotic activity. This property is due to an active participation of endothelial cells in the inhibition of platelet adhesion and aggregation, in the inhibition of thrombin generation, in the direct inactivation of thrombin, and in clot lysis through the fibrinolytic system. When endothelial cells are stimulated by cytokines such as tumor necrosis factor (TNF) or interleukin 1 (IL-1), they may switch to an active procoagulant state. On the one hand, thrombin generation can be regulated on the endothelial cell surface by thrombomodulin,…which allows the activation by thrombin of protein C which subsequently acquires and expresses potent anticoagulant properties. On the other hand, after activation, the same endothelial cell can express tissue factor on its surface, which will lead to the triggering of the coagulation cascade resulting in the generation of thrombin. TNF has been shown both to induce tissue factor gene expression and to suppress transcription of the thrombomodulin gene in endothelial cells. Many cytokines induce tissue factor gene expression and procoagulant activity in the monocyte/macrophage lineage; they also stimulate adhesion of leukocytes to endothelial cells. Cytokines such as IL-1 or TNF can thus be characterized as important intercellular messengers during the onset of coagulation. The role of these compounds can be schematized as: 1) agents of the stimulation of endothelial cells by leukocytes, 2) agents of stimulation of leukocytes by endothelial cells, 3) localization of the coagulation response through the initiation of endothelial cell-leukocyte interactions. Pharmacological modulation of these responses is possible along two pathways: 1) inhibition of the activation of endothelial cells or leukocytes responsible for cytokine release, 2) inhibition of the cytokine-induced cellular activation responsible for potentiation of procoagulant activity.
Abstract: Mucins, are densely packed in secretory granules of goblet cells. Upon exocytosis they undergo massive hydration that results in the formation of the mucus gel. Because the mucin polymer network is held together by tangles and low energy bonds, the rheological properties of this gel are mainly determined by the degree of postexocytotic hydration. Hydration in mucus is governed by a Donnan equilibrium as it is driven by electrostatic interaction among the polyionic charges of the mucins and other fixed polyions. Although, variations of charge density of the mucin polymer could be an efficient physiologic mechanism to control the rate…of mucus hydration and rheology, this subject has not been investigated. In here we describe a primary tissue culture system of cervical goblet cells of the monkey uterus. This preparation allows to measure directly the kinetic of hydration of exocytosed mucins. Because the physicochemical parameters of the bathing medium can be effectively controlled, variations in the kinetic of mucins swelling upon exocytosis, can be used as a convenient indicator of fluctuations of charge density in secretory products. Since the cervical mucosa readily respond to endocrine influences, this preparation can provide a useful model to study the effect of hormones or other transmitters on polyionic charge density of secretory product.
Abstract: A λ gt11 cDNA library constructed from human tracheal mucosa was screened with rabbit antibodies raised to chemically deglycosylated pronase glycopeptides from bronchial mucins. This library allowed us to select 20 positive clones. The total or partial nucleotide sequences of 14 of them were classified in three different types of organization or families. Antibodies purified from total immuneserum on each positive clone were specific either of goblet cells or goblet cells and mucous cells, showing a differential cellular expression of the peptide axis of mucins. The use of each type of nucleic probe in Northern blot analysis confirmed the…existence of a great heterogeneity of the RNAs contributing to a great peptide heterogeneity.
Keywords: Mucins, cDNA library, peptide organization, Northern blot analysis
vol. 27, no. 3-4, pp. 471-484, 1990
Abstract: The molecular mechanisms mediating mucous cell metaplasia and hypersecretion in the respiratory tract are unknown. Previous work suggests that mucous metaplasia requires the induction of mucin gene expression. We are investigating this possibility by monitoring steady state levels of mucin mRNA in a model of mucous cell metaplasia induced by SO2 exposure. Male Sprague Dawley rats were exposed to 400 ppm SO2 gas in air for 3h per day, 5 days per week for 0,1,2, or 3 weeks. Sham controls were exposed to air under similar conditions. After 3 weeks, morphological changes were apparent in the epithelium of…SO2 exposed rats at all levels from the trachea to the distal airways. The epithelial thickness increased, as well as the number and size of glands in the trachea. Epithelial mucous (goblet) cells increased from 0 to 4.5 per rom in the trachea, 0.2 to 6.2 per rom in the main stem bronchi, and 0.2 to 22.7 per rom in the distal airways (mean values obtained for 3-6 tissue blocks per airway level per condition). In parallel experiments, we used SMUC 41, a 950 bp human intestinal cDNA to isolate a human airway cDNA, HAM-1 from a cDNA library constructed in bacteriophage from human bronchial poly A+ RNA. HAM-1 is a 90 bp cDNA encoding a threonine- and proline-rich peptide with 96% homology to the human intestinal cDNA SMUC-41. Next we probed total and poly A+ airway RNA from rats in each exposure condition with SMUC-41 or HAM-1. Blots were then stripped and reprobed with a cDNA encoding beta actin. Densitometry values normalized for the amount of RNA loaded per lane (as determined by actin hybridization intensity) showed that mucin mRNA increased 8-9 fold as a function of SO2 exposure. This is consistent with the possibility that mucin gene transcription is induced by SO2 exposure, and may represent a primary event in the development of mucous metaplasia and hypersecretion.
Abstract: Confluent cultures of hamster tracheal surface epithelial (HTSE) cells are highly enriched with secretory cells and secrete mucins. Ultrastructural studies of cellular localization of these mucins show that mucins are found not only inside secretory granules but also on the apical surface of secretory cells during active secretion, and secreted mucins are highly associated with lipids. In the present communication, we analyzed lipids associated with both cellular and secreted mucins following metabolic radiolabeling of these cultured cells with [3 H]palmitic acid. We found that profiles of lipids associated with both cellular and secreted mucins are almost identical not only qualitatively…but also quantitatively. It is concluded that the lipid association with mucins seems to take place before secretion. The origin of the cell surface-bound mucins is discussed.
Keywords: Mucin, lipid, tracheal, goblet cell
vol. 27, no. 3-4, pp. 491-501, 1990
Abstract: The wettability of poly(methyl methacrylate) and polyethylene by water and aqueous mucin solutions have been studied by sessile drop and under-water captive air bubble contact angles, respectively. From the sessile drop and octane under-water contact angles the polymer-water interfaces have been characterized in terms of works of adhesion and acid-base (polar) interactions. A large water-air contact angle hysteresis observed with poly(methyl methacrylate) surfaces has been attributed to side-chain B relaxations of polymer ester methyl groups. The wettabilities of the polymers by mucin aqueous solutions have been studied as a function of protein concentration and related to the surface tensions. A…positive slope of adhesion tension vs surface tension line, characteristic of polar surfaces, was found with poly(methyl methacrylate). By contrast, a change in the slope, explained as a change in mucin relative adsorption densities at solid/liquid and solid/vapour interfaces, was observed with polyethylene. This adhesion tension behavior appeared to be in agreement with previous data we have published concerning the quantity and state of mucin which are adsorbed to polymers characterized by different surface properties.
Abstract: The transepithelial potential difference (PD) value represents an integral of ion fluxes across the epithelium, and relates to the regulation of airway fluid. We studied six healthy two day old husky puppies for their tracheal mucus rheology and bioelectric properties, since this data in newborns are still unknown. PD (-mV, epithelium vs. subcutaneous space) was measured using the agar bridge technique in two locations - lower trachea and subglottic region. For the rheological analysis, the magnetic microrheometer was employed; data are presented as mechanical impedance log G* and loss tangent tan δ (1 rad/s). The mucus collection rate (mg/min)…and the solid content (%) were determined by gravimetry. Mucociliary clearability, normalized to frog mucus, (MCFP) was determined directly by the frog palate method; a cough clearability index (CCI) was computed from simulated cough machine data obtained with mucus-like gels. The mucus collection rates and PD values were considerably lower than those observed in adult dogs; the mechanical impedance values were also reduced in comparison with adult data. The PD profile (-13.9 ± 1.2 mV lower trachea vs. -18.4 ± 1.4 mV subglottical, i.e. more negative subglottically), however, is similar to that observed in adult dogs. Intratracheal profiles in mucus collection rate and mucus rheology were also comparable between puppies and adult dogs. The low collection rates in puppies, particularly in lower trachea, could indicate either reduced mucus volume or slower clearance. PD and collection rate correlated very strongly (r = 0.82, p = 0.0003). PD also correlated negatively with log G* (r = 0.73, p = 0.003) and positively with tan δ (r = 0.58, p = 0.03). MCFP and % solids correlated positively (r = 0.84, p = 0.0012), in contradistinction to the usual relationship, perhaps due to the presence of non-glycoprotein components that do not contribute to crosslink formation. The apparent maturation of airway bioelectric properties, mucus collection rate and mucus viscoelasticity are all consistent with the maturation of mucociliary clearance, which has previously been reported.
Abstract: The cilia that propel mucus are specialised for the function in their arrangement length, some details of structure, beat pattern, beat cycle characteristics, metachronal coordination, local control of beat rate by response to mechanical stimulation and generalised control of beat rate by neurohormones. These features are matched to the properties of the visco-elastic mucus gel that is propelled at the ciliary tips above a low-viscosity periciliary layer whose depth must be regulated within defined limits.
Abstract: A computer-assisted transillumination, photoelectronic technique has been used to measure the beat frequency of cilia of rabbit tracheal cells grown in culture. When ciliated cells arc mechanically stimulated with a microprobe the cells respond rapidly by increasing the beat frequency of their cilia. This mechanosensitive response is not limited to the stimulated cell, but is communicated in all directions to neighboring cells. To characterize the progression of this communicated response we used an automated computer-assisted imaging system to examine high-speed films of responding cells. The time it takes for the response to be transmitted between cells is slow (1-3 sec)…with each cell responding after a lag-time that is proportional to the distance of the cell from the stimulated cell. We have confirmed that gap junctions are present between cells and that adjacent or non-adjacent ciliated, as well as non-ciliated, cells are electrically coupled. To correlate the mechanosensitive response with intracellular calcium fluxes we have used fura-2, a calcium-specific fluorescent dye, and digital video microscopy. Mechanical stimulation of the cultured ciliated cells, in the presence of extracellular calcium, resulted in an initial increase in intracellular calcium, which was communicated to neighboring cells. Without extracellular calcium, mechanosensitivity of cultured cells was lost and a small decrease in intracellular calcium was observed in the stimulated cell. However, neighboring cells still displayed an increase in intracellular calcium. The time course and general pattern of calcium increase in adjacent cells was similar to the responses in ciliary activity produced by mechanical stimulation. Ciliary beat frequency is also elevated by f3-adrenergic drugs independently of mechanosensitivity. These responses are important because they could provide a dual regulatory mechanism for the control of mucus transport. Adrenergic agonists could provide non-specific control by increasing ciliary activity throughout the airways while mechanosensitivity could provide local control by increasing activity in those regions of heavy mucus load.
Keywords: Cilia, Mechanosensitivity, Intracellular calcium, Intercellular communication
vol. 27, no. 3-4, pp. 533-545, 1990
Abstract: Ciliary metachronism and motility were examined optically in muco-ciliary tissue cultures from three different systems: a) frog’s palate epithelium, b) frog’s oesophagus, and c) human nasal polyps. In addition, lateral cilia of Mytilus edulis (water transporting cilia) were examined. It was revealed that the degree of synchronization between muco-ciliary systems is lower than that of water transporting cilia. There are no significant differences between different muco-ciliary systems, within the accuracy of of measurement although relatively large statistical ensembles were used. In addition the wavelength and wave direction of the metachronal wave was examined. All four systems exhibit similar wavelength. The…metachronal parameters of muco-ciliary systems exhibit fluctuations (as was demonstrated by the degree of synchronization), however, the magnitude and repetitivity of these fluctuations, is dependent on the loading of the ciliary system. We have loaded the system by increasing the viscosity of the medium. Under viscous load the frequency of the beating decreased. The metachronal wavelength became longer and the metachronal coordination type more orthoplectic.
Abstract: Primary cultures of respiratory epithelium were produced as outgrowths from human fetal and adult tracheal and nasal polyp explants. Video recordings of the epithelial cell outgrowths were carried out after 5 days of culture and the ciliary beating frequency was analyzed by using a video technique. Uniform fields of differentiated ciliated cells were observed near the edge of the explant. In the transition region of the outgrowth from the explant to the outgrowth periphery, isolated ciliated cells were present, as well as cells with fused cilia. The ciliary beating frequency of the outgrowth of well-differentiated ciliated cells (13.5 ± 1.4…Hz) was significantly higher (p < 0.001) than the beating frequency of both the explant (11.9 ± 0.7 Hz) and the ciliated cells with fused cilia (9.8 ± 1.7 Hz). The same differentiation stages and functional activities were observed in the outgrowth cultures, whatever their origin. These in vitro models are comparable with each other and therefore could be useful for studying the ciliogenesis and functional activity of the human respiratory epithelium.
Keywords: Cell culture, tracheal outgrowth, nasal outgrowth, ciliary frequency
vol. 27, no. 3-4, pp. 559-565, 1990
Abstract: A new automated method of image analysis of sperm flagellar (human) and cilia (Dunaliella) bends is developed. This method permits an automatic determination of the line characterizing the flagellum. Two dynamic parameters are measured: the wave propagation velocity and the wave curvature radius. The data reveal similar patterns in the propagation of the principal and reverse waves between flagelated and ciliated cells. Conversely, differences are seen in principal wave curvature due perhaps to the presence of periaxonemal structures in the flagellum, absent in cilium. The identical patterns of reverse wave curvature in both systems may be linked to axonemal limitations.
Abstract: Plasma viscosity is elevated in various pathological states, due to increased levels of protein and other macromolecules. The possibility that elevation of extracellular fluid viscosity (EFV) affects cellular and biochemical functions was examined in cultured liver cells and in red blood cells. The viscosity was modified by the addition of various macromolecules, which differ in their capacity to increase viscosity and in their chemical nature. It was found that secretion of lipoproteins and lysosomal enzymes by liver cells is inhibited as a function of the medium viscosity. Correspondingly, elevation of plasma viscosity of hyperlipidemic rats reduced lipoprotein levels. In search…for the mechanism of this phenomenon we examined the effects of EFV on two cell membrane components which are involved in transmembrane processes: Gangliosides (GMs) , and phospholipase A2 (PLA2). It was found that the rate of GMs degradation is decreased with increasing EFV. Of special interest was the finding that the activity of cell membrane PLA2, a key enzyme in secretory processes, is inhibited by increasing EFV. This phenomena was not confined to cell membrane PLA2, as we further found that erythrocyte hemolysis, induced by soluble snake venom PLA2, is inhibited as the EFV is increased. It is proposed that the extracellular fluid viscosity may play an important role in regulation of cellular and biochemical processes in general.
Abstract: The effects of alterations in blood and plasma viscosities on plasma renin activity (PRA) were studied in dogs anesthetized with pentobarbital. Blood viscosity was altered by changing the hematocrit (Hct) level by isovolemic exchange using packed red blood cells or plasma. Plasma viscosity was elevated by isovolemic exchange using Hct-matched blood with high molecular weight dextran (Dx, mean m.w. ∼450,000) dissolved in plasma. Following control measurements of plasma and blood viscosities, plasma [Dx], PRA, Hct and hemodynamic functions, the dog was subjected to isovolemic exchange transfusions to either alter the Hct or administer the Dx. Various measurements were repeated 40–60…min after each exchange. Arterial pressure and renal blood flow remained relatively constant after exchanges; increases in plasma and blood viscosities were accompanied by a decrease in renal vascular hindrance (vasodilation) to keep the renal flow resistance at control level. PRA rose with increases in plasma [Dx] and viscosity, and the rise in PRA was best correlated with the decrease in renal hindrance. The changes in PRA and renal hindrance have the same regression line whether blood viscosity was altered by Hct variation or Dx administration. The results indicate that increases in viscosity cause a compensatory vasodilation of renal vessels to cause renin secretion.
Abstract: Investigations of Myoglobin, Hemoglobin and, more recently of Hemerythrin, suggest that the inward and outward motion of the oxygen ligand is governed by fluctuations between open and closed paths in the protein and that the driving force is the local brownian motion of protein residues. Reaction rates involving protein internal motions are strongly influenced by the viscosity of the sol vent, whereas the ultimate binding of oxygen at the protein’s active site remains viscosity independent. The description of a protein reaction therefore requires the introduction of a free energy surface with a conformation coordinate accounting for the viscosity-dependent protein transitions…in addition to the usual reaction coordinate which only describes the system of reactants in a fixed protein conformation.
Keywords: Hemoproteins, Hemerythrin, geminate recombinations, protein dynamics
vol. 27, no. 3-4, pp. 599-604, 1990
Abstract: Solvent viscosity is known to play an important role in the kinetics of biochemical reactions, and has been suggested to modulate the dynamic structure of proteins. The effect of viscous cosolvents, of various molecular sizes, on the apparent ultrasonic absorption of bovine serum albumin in solution, at 37°C, has been measured in attempt to investigate the following phenomena: 1) The predicted modulating effect of viscous cosolvents on the “internal friction” of proteins, and 2) possible differences between the microscopic and macroscopic pictures of the solvent viscosity concerning the proposed effect. We have found that A) The absorption of ultrasound (3–17…MHz) by the protein increases with increasing the cosolvent concentration. B) That increase correlates with the solvent viscosity for small cosolvent molecules, but not with macromolecular cosolvents, and C) Dextran solutions with the same concentration by weight, reveal similar ultrasonic absorption, in spite of large differences in their viscosity. A possible explanation is discussed.
Keywords: viscosity, mixed solvents, proteins, ultrasonic absorption, dextran, protein dynamics
vol. 27, no. 3-4, pp. 605-610, 1990
Abstract: The area neglected so far in the fields of clinical and theoretical haemorheology is that of interact ion between viscosity and chemical reactions in the cells. The reintroduction of teinochemical principle opens entirely new doors for investigation both in vitro and in vivo. Effect of extracellular fluid viscosity on synthesis (i.e. lipids) and on possible enzymatic and catalytic functions influences our opinion that haemorheology has to go back to fundamentals.
Keywords: teinochemical principle, viscosity and chemical reaction
vol. 27, no. 3-4, pp. 611-616, 1990