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Biomedical subjects

D Gingell

Publications and source records attributed to D Gingell.

At least 37 records · Page 2Linked to original sources

Conformational response of the glycocalyx to ionic strength and interaction with modified glass surfaces: study of live red cells by interferometry.

We have measured separation distances between live human red blood cells and simple or modified glass surfaces, using the finite aperture technique of microscope interferometry. In general, separation increases as the ionic strength falls, in isotonic solutions. Restriction on movement parallel to the glass in all except the most dilute salt solutions, coupled with the absence of Brownian motion, indicates direct molecular contact with the substratum. Thus increased separation must be due to swelling of the glycocalyx under electrostatic forces. However, at approximately less than to 2mM adherent cells show a separation greater than 100 nm, execute Brownian motion and the restriction on lateral motion is less evident. This suggests that secondary minimum adhesion by long-range forces with little or no direct molecular connection occurs at extreme dilution only. Treatment of cells with trypsin reduces separation by up to 40 nm, but the extent to which this reflects reduced double-layer repulsion due to loss of surface charge, as opposed to the reduced opportunity for swelling in a trimmed-down glycocalyx, is unclear. Adhesion at a separation approximately 100 nm in 1 mM buffer after trypsinization supports the view that adhesion can occur without very long glycoprotein connections, but does not prove it. Adhesion to unwettable methylated glass and completely wettable unmethylated glass, with an identical ionic strength dependence of the separation, shows that hydrophilicity is not an absolute requirement. Red cells interact closely at all ionic strengths with glass made polycationic with poly-L-lysine, owing to electrostatic attraction. The interference technique also shows that adherent cells can be spaced from the glass by an intervening layer of previously absorbed serum albumin.

Cell Adhesion↗

A sharp cell surface conformational transition at low ionic strength changes the nature of the adhesion of enzyme-treated red blood cells to a hydrocarbon interface.

Aldehyde-fixed human red cells have previously been used to assess the roles of electrostatic and electrodynamic forces in adhesion. We have attempted to test the prediction that enzymic removal of cell surface negative charges should increase adhesion in dilute salt solutions by reducing electrostatic repulsion. While this is indeed the case for neuraminidase-treated cells and also for Pronase- and trypsin-treated cells over much of the low ionic strength range, the latter two treatments cause very strong adhesion over a remarkably narrow range of ionic strength centred on 1 mM-NaCl. At 0.5 and 1.5 mM adhesion is negligible. After Pronase treatment a further adhesive peak occurs at 2.5 mM. Electrophoresis of protease-treated cells shows small but clear reductions in mobility at precisely these peak adhesion values. These electrophoretic potential changes are almost certainly not large enough to cause increased adhesion directly, and it is thought that they are second-order changes, symptomatic of a structural rearrangement of the cell surface. How this causes such vastly augmented adhesion is an intriguing problem.

Cell Adhesion↗

Interaction between intracellular vacuoles and the cell surface analysed by finite aperture theory interference reflection microscopy.

Using finite aperture theory we have shown that localized very dark areas in the interference reflection images of Dictyostelium discoideum amoebae are due to the close intracellular approach of vesicles and tubular elements of the contractile vacuole system to the plasma membrane adjacent to the substratum. Vesicles interacting in this way become locally deformed to the planar contour of the substratum and are separated from the cell surface membrane by a constant approximately less than 0.1 micron of cytoplasm. Lamellar processes formed by these cells on very adhesive surfaces have identical dimensions. This minimal thickness may be a mechanical consequence of a contractile mechanism which pulls membranes together.

Animals↗

The interpretation of interference-reflection images of spread cells: significant contributions from thin peripheral cytoplasm.

In interference-reflection microscopy, used for investigating cell-substratum separation, it is commonly believed that cytoplasmic thickness can be ignored, provided a high illuminating numerical aperture (INA) is used. It is shown here that even when a maximal INA is used, cytoplasmic lamellae of I micrometer or less can be major determinants of the image. The leading lamella of spreading tissue cells and large peripheral areas of Dictyostelium discoideum amoebae on adhesive substrata are less than I micrometer thick and it is argued that hitherto unexplained features of the interference images of these cells may be interpreted in terms of the theory used here.

Cytoplasm↗

Red blood cell adhesion. I. Determination of the ionic conditions for adhesion to an oil-water interface.

We have examined the adhesion of glutaraldehyde-treated human red blood cells to a clean liquid hydrocarbon interface as a function of sodium chloride concentration. Cells adhere reversibly to the interface over a wide range of concentrations but fail to do so below about 0.1 mM. Adherent cells do not alter the tension of the oil/water interface. These results show that cells can adhere by physical forces in special situations without biochemical interactions. The data provide a basis for calculating the size of the physical forces.

Alkanes↗

Red blood cell adhesion. II. Interferometric examination of the interaction with hydrocarbon oil and glass.

Using both living and glutaraldehyde-fixed red cells, we have examined adhesion to both oil/saline and glass/saline interfaces by interference reflection microscopy. At low ionic strength, 0.4 mM NaCl, fixed cells adherent to the oil/saline interface show first order whitish yellow zones of closest approach which indicate a separation of similar to or approximately 100 nm. Quantitative interferometry in monochromatic light supports this conclusion. As the salt concentration is increased the separation decreases and the final image shows zero-order black which probably indicates molecular contact with the interface. Similar but less reproducible results were obtained with fixed and unfixed cells on glass. Thes observations show that physical interactions alone can be responsible for adhesion in dilute and concentrated salt solutions. It is not, however, believed that the results necessarily imply the existence of adhesion with a gap in physiological concentrations of salt.

Alkanes↗

Red blood cell adhesion. III. Analysis of forces.

The results of experiments on the adhesion of glutaraldehyde-fixed red blood cells to both polarizable metal/saline and liquid hexadecane/saline interfaces have been analysed in terms of physical forces. The results show that the electrostatic repulsions sufficient to prevent adhesion to these test surfaces are remarkably similar, and that a force-balance condition is predicted at cell-substratum separations similar to or approximately 100 nm in 0.4 mM NaCl as found by interferometry. From the repulsive force the size of the attractive force can be found. If this is viewed as an electrodynamic attraction, the force coefficient is found to lie between 5 and 8 x 10(-14) erg (5 and 8 x 10(-21)J), a range in reasonable correspondence with measurements in physical systems.

Alkanes↗

Interference reflection microscopy. A quantitative theory for image interpretation and its application to cell-substratum separation measurement.

We propose a quantitative theory of microscope interferometry where the specimen is illuminated by a cone of monochromatic light of solid angle 0 - 100 degree, corresponding to an illuminating numerical aperture of 0 to approximately 1.2. Computed results compare favorably with photometric measurements of fringe irradiance for a water wedge 0 - 2,000-nm thick. The interpretation of cell-substratum interference images is discussed in relation to the theory. We conclude that in assessing cell-glass separation, the cytoplasmic thickness does in general contribute significantly to the final image, but this contribution is minimized at high illuminating apertures. In these circumstances, however, normal incidence theory is inapplicable and the theory for finite illuminating aperture is essential. Neglect of this fact can lead to errors of up to 100% in estimated cell-glass separation.

DNA↗

Scanning electron-microscopic study of the uptake of Leishmania parasites by macrophages.

The interaction of promastigotes of the protozoan parasite Leishmania tropica with mouse peritoneal macrophages in vitro was studied by scanning electron microscopy. Motile promastigotes attached to host cells by their flagellar tips to which the macrophages responded by producing rather closely fitting lamellar sheaths and progressively enveloping first the flagellum and then the body of the parasite. Lamellar advance during engulfment was rapid in the first 10 min but much slower later on. Fully engulfed parasites could be seen after 1 h but most parasites associated with host cells remained extracellular even after 4 h. On the other hand, parasites immobilized by fixation adhered by either their flagellar or somatic ends. Engulfment proceeded at a steady rate, and by 4 h most of them were completely engulfed. Both the attachment and engulfment stages of parasite uptake were inhibited by low temperature, cytochalasin D and mild fixation of macrophages. The rheological features of the host cells' response to parasite adherence indicate that invasion by parasites is through phagocytosis rather than penetration.

Animals↗

Apparent modification of forces between lecithin bilayers.

Small sugar solutes effect variation in the equilibrium separation of lecithin bilayers in aqueous solution. Since sugars have negligible influence on bilayer structure, they probably act by modifying interbilayer forces. The observed widening and narrowing of the bilayer separation is correlated with the predicted weakening and strengthening of the attractive van der Waals forces between lipid bilayers that occurs with increasing sugar concentrations.

Chemical Phenomena↗

Interaction of red blood cells with a polarized electrode: evidence of long-range intermolecular forces.

We have investigated the electrostatic interaction of glutaraldehyde-fixed human red cells with a polarizable electrode carrying a defined surface charge density which can be varied continuously through a wide range. Cells in a dilute salt solution are unable to adhere to the electrode at high negative charge, but at lower negative charge densities they are reversibly adherent and can be forced off by increasing the negative polarization. Near zero electrode charge they become irreversibly stuck to the electrode and cannot be evicted even at maximum electrode polarization. Calculation of the electrostatic repulsive force using measured charge densities indicates the existence of an attractive force which may be acting over several hundred angstroms.

Cell Adhesion↗

Adhesion of red blood cells to charged interfaces between immiscible liquids. A new method.

We have devised a method of making a flat oil/water interface which remains flat on inversion. Cell adhesion to the interface can be observed microscopically. Glutaraldehyde-fixed human red blood cells adhere to the interface between physiological saline and hexadecane containing surface-active behenic acid at pH values below about 7-5. At high pH values, cells are prevented from adhering due to dissociation of the carboxyl groups of behenic acid oriented in the interface. The negative red cells are driven away electrostatically. Adherent and non-adherent cells remain on the aqueous side of the interface and do not appreciably deform it when adherent. Cells are electrostatically attracted to a similar interface containing positively charged octadecyltrimethylammonium ions. Cells also adhere to an interface containing octadecanol, which carries no charge. Underlying both electrostatic repulsion and attraction between red cells and oil/water interfaces is an attractive force which may be of electrodynamic (van der Waals) origin.

Cell Adhesion↗