Biorheology - Volume 24, issue 6

Authors: King, Malcolm

Article Type: Research Article

Abstract: The relationships between mucus rheology, depth of mucus layer and clearance by simulated cough were examined in a study employing a model plexiglass trachea lined with gels formed from locust bean gum crosslinked with sodium tetraborate. The viscoelastic properties of the mucus simulants were determined by magnetic rheometry at 100 rad/s and expressed as mechanical impedance (dynamic stress/strain ratio) and loss tangent. Cough was simulated by opening a solenoid valve connecting the model trachea to a pressurized tank, using an upstream flow-constrictive clement to shape the flow profile to approximate the pattern seen in a normal adult. Mucus clearance was …quantitated by observing the movement of contrasting marker particles placed in the mucus layer. The median particle displacement was defined as the clearance index, Cl . For any initial depth of mucus, Cl increased with driving pressure in the tank, and for a given driving pressure, Cl increased linearly with increasing mucus depth. For a given driving pressure and depth, Cl decreased with increasing mechanical impedance of the mucus. At constant mechanical impedance, Cl increased with increasing loss tangent, in other words, cough clearance was impeded more by elasticity than viscosity. Mucus clearance was associated with transient wave formation in the lining layer. Thus dependence on viscoelasticity is consistent with observations that airflow-mucus interaction and wave formation are impeded by elasticity. The clearance vs . loss tangent relationship for cough is opposite to that found for ciliary clearance (Biorheology 1980, 17, 249), suggesting a natural balance in viscosity and elasticity for mucus to be cleared by both mechanisms. The differences in clearance-viscoelasticity relationship also suggest that rheological adaptation of mucus should occur when the mode of clearance shifts from ciliary action to cough. Show more

Keywords: mucus rheology, two-phase flow

DOI: 10.3233/BIR-1987-24611

Citation: Biorheology, vol. 24, no. 6, pp. 589-597, 1987

Authors: Priel, Zvi

Article Type: Research Article

Abstract: Recently a computerized electro-optical method was developed which enables one to simultaneously measure the frequency and the wavelength of the metachronal waves in beating cilia. The method is based on measurement of scattered light from two areas at a given distance apart. The distance between measured areas can be varied from zero to hundreds of microns. The relative ease of the measurement and data analysis of this method enable one to create large statistical ensembles in order to obtain reliable averages. In this work we show that in addition to the previously mentioned parameters this system can measure directly …the velocity of the metachronal wave. It was found that the average velocity in the tissue culture from frog’s palate epithelium at room temperature is ∼ 270 μ m/sec, about twice the average particle velocity at the frog’s palate. Show more

Keywords: muco-ciliary transport, metachronal wavelength, metachronal velocity

DOI: 10.3233/BIR-1987-24612

Citation: Biorheology, vol. 24, no. 6, pp. 599-603, 1987

Authors: Silberberg, A.

Article Type: Research Article

Abstract: An approximately 500,000Da subunit characterizes the structural glycoprotein of mucus. This unit is composed of a rod-like very heavily glycosylated protein chain with an unglycosylated cysteine rich region at its end. It is proposed that the ‘bare’ peptide portion of the subunit forms itself into a lectin by undergoing a disulfide bond stabilised conformational fold. The lectin binding site, R, is assumed to be selective for a rare sugar sequence, which, when present, creates a binding site R*. The site R* has to be relatively rare. The average number <s*> of sidechains which contain R* per subunit will only be …of order 1. When <s*> ⩽ 1 reasonably long, chain-like aggregates are formed which behave like coiling polymer chains with the subunit the Kuhn statistical element. When <s*> > 1 the entire system forms one structure. Data obtained from the literature are analysed. They favor finite size, separate chains. The Kuhn statistical element length, derived from the data, is shown to agree well with the lectin model hypothesis. Show more

Keywords: Mucus glycoprotein, mucus glycoprotein subunit, mucus dissolution, lectin, disulfide bond

DOI: 10.3233/BIR-1987-24613

Citation: Biorheology, vol. 24, no. 6, pp. 605-614, 1987

Authors: Sellers, L.A. | Allen, A. | Morris, E.R. | Ross-Murphy, S.B.

Article Type: Research Article

Abstract: Mechanical spectroscopy has been used to study the structure of mucus gel taken from the surface of the pig gastrointestinal tract. Mucus from stomach, duodenum and colon was insoluble and its mechanical properties, characteristic of a weak viscoelastic gel, were unchanged in saline, acid (pH 2) and denaturants. Small intestinal mucus gel which was of poorer quality, was disrupted following exposure to acid and denaturants. Concentration of purified glycoprotein produced gels that had mechanical spectra with the same profiles as the respective native secretion except for reconstituted small intestinal mucus which was of better quality and similar to the other …native and reconstituted gels. Reduction of S-S linkages or proteolysis of all mucus gels caused a collapse of structure to give profiles typical of a viscous solution. This collapse of gel structure was shown to result from a breakdown of the covalent polymeric structure of the component glycoproteins. A linear correlation for mucus gels was observed between gel quality (as defined by tan δ ) and the ratio of polymeric glycoprotein to its degraded lower molecular weight subunit. Human gastric mucus from a histologically normal stomach also had the characteristics of a weak viscoelastic gel, although that from patients with peptic ulcer disease has a significantly reduced content of polymeric glycoprotein. Show more

Keywords: gastrointestinal mucus, mechanical spectroscopy, peptic ulcer, glycoprotein polymeric structure

DOI: 10.3233/BIR-1987-24614

Citation: Biorheology, vol. 24, no. 6, pp. 615-623, 1987

Authors: Verdugo, P. | Aitken, M. | Langley, L. | Villalon, M.J.

Article Type: Research Article

Abstract: Mucin-containing granules, produced by mammalian goblet cells in vitro , undergo massive post-exocytotic swelling (23). Their swelling kinetics are similar to the swelling of condensed artificial polymer gels (22). Earlier, we proposed that mucins are condensed in the secretory granule and expand by swelling during or after exocytosis (21). The swelling of mucus is affected by ionic influences, as it is governed by a Donnan equilibrium process (21). However, the effect of cations on the swelling of newly released mucins had not yet been investigated. Calcium has been found in high concentration inside secretory granules of mucin-secreting cells (18, 9, …25), and is also elevated in the mucus of cystic fibrosis patients (17). The present experiments were designed to study the effect of extracellular Ca++ concentration on the swelling kinetics of the newly released secretory product of respiratory goblet cells in vitro . The data show that extracellular Ca++ , in concentrations similar to those found in the mucus of cystic fibrosis patients (2 to 4 mM) can produce a four-fold decrease in the diffusivity of the newly released mucin polymer network, resulting in a slow rate of swelling, and a mucus that remains thick for long periods of time. The present findings are in agreement with the Donnan equilibrium hypothesis for the regulation of mucus swelling and rheology (21), and bear important implications for the pathophysiology of cystic fibrosis. Show more

Keywords: Mucus swelling, Donnan effect, exocytosis, polymer network, Ca++, cationic shielding

DOI: 10.3233/BIR-1987-24615

Citation: Biorheology, vol. 24, no. 6, pp. 625-633, 1987

Authors: Winet, H.

Article Type: Research Article

Abstract: Observations of flow velocity profiles over frog mucociliated palate are used to estimate viscosity, shear rate and shear stress in the periciliary flow field. The ability of cilia to generate significant shear stress at long distances and their utility as rheometers are examined. It is proposed that the depth of significant ciliary shear penetration into the periciliary fluid is sufficient to move mucus masses well beyond the ciliary tips, obviating the need for tip penetration where anchoring phenomena are sufficiently reduced.

Keywords: mucociliary transport, periciliary fluid, frog palate, mucus viscosity, mucus flow, velocity profiles

DOI: 10.3233/BIR-1987-24616

Citation: Biorheology, vol. 24, no. 6, pp. 635-642, 1987

Authors: Kwiatkowski, D.J. | Yin, H.L.

Article Type: Research Article

Abstract: Gelsolin is a Ca2+ -binding protein of mammalian leukocytes, platelets and other cells which has multiple and closely regulated powerful effects on actin. In the presence of micromolar Ca2+ , gelsolin severs actin filaments, causing profound changes in the consistency of actin polymer networks. A variant of gelsolin containing a 25-amino acid extension at the NH2 -terminus is present in plasma where it may be involved in the clearance of actin filaments released during tissue damage. Gelsolin has two sites which bind actin cooperatively. These sites have been localized using proteolytic cleavage and monoclonal antibody mapping techniques. The NH2 -terminal …half of the molecule contains a Ca2+ -insensitive actin severing domain while the COOH-terminal half contains a Ca2+ -sensitive actin binding domain which does not sever filaments. These data suggest that the NH2 -terminal severing domain in intact gelsolin is influenced by the Ca2+ -regulated COOH-terminal half of the molecule. The primary structure of gelsolin, deduced from human plasma gelsolin cDNA clones, supports the existence of actin binding domains and suggests that these may have arisen from a gene duplication event, and diverged subsequently to adopt their respective unique functions. The plasma and cytoplasmic forms of gelsolin are encoded by a single gene, and preliminary results indicate that separate mRNAs code for the two forms. Further application of molecular biological techniques will allow exploration into the structural basis for the multi functionality of gelsolin, as well as the molecular basis for the genesis of the cytoplasmic and secreted forms of gelsolin. Show more

Keywords: Actin, Actin-binding proteins, DNA, Gelsolin, Molecular biology, Monoclonal antibody

DOI: 10.3233/BIR-1987-24617

Citation: Biorheology, vol. 24, no. 6, pp. 643-647, 1987

Authors: Coller, Barry S.

Article Type: Research Article

Abstract: The interaction of platelets with natural and artificial surfaces is briefly reviewed, emphasizing the role of the platelet glycoprotein Ib and IIb/IIIa receptors. Studies utilizing monoclonal antibodies to these receptors for the diagnosis and therapy of hemorrhagic and thrombotic disorders are described, indicating the potential of such agents as platelet inhibitors.

Keywords: Platelet, Fibrinogen, GPIb, GPIIb/IIIa Monoclonal Antibody

DOI: 10.3233/BIR-1987-24618

Citation: Biorheology, vol. 24, no. 6, pp. 649-658, 1987

Authors: Chien, Shu

Article Type: Research Article

Abstract: This presentation is aimed at giving some background information on molecular biology, thus serving as an introduction to the symposium on Molecular Biorheology held during the sixth International Congress of Biorheology in Vancouver. The papers presented at this Symposium indicate that the use of molecular biological techniques allows the understanding of normal and abnormal rheological properties of cells and organs at the molecular level. It is hoped that these examples will provide an impetus for us to open new frontiers of research in biorheology by taking advantage of the powerful tools developed from recent advances in molecular biology.

Keywords: DNA, Erythrocytes, Gelsolin, Gene cloning, Molecular biology, Platelets, RNA

DOI: 10.3233/BIR-1987-24619

Citation: Biorheology, vol. 24, no. 6, pp. 659-672, 1987

Authors: Conboy, John

Article Type: Research Article

Abstract: The application of molecular biology to the study of the human erythrocyte membrane is presented in this report. We describe the strategy employed to clone DNA sequences encoding the membrane skeletal protein, protein 4.1. We demonstrate how these sequences may be utilized to deduce detailed structural and functional information about the 4.1 polypeptide. We also illustrate the use of cloned 4.1 DNA sequences as probes to explore the structural organization of the protein 4.1 gene in normal individuals and in patients with dysfunctional erythrocyte membranes. Ultimately it will be possible to generate a molecular description both of the structural proteins …which constitute the membrane skeleton, and of the genetic mechanisms regulating their expression in erythroid and nonerythroid cells. Show more

DOI: 10.3233/BIR-1987-24620

Citation: Biorheology, vol. 24, no. 6, pp. 673-687, 1987