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Biomedical subjects

H E Stanley

Publications and source records attributed to H E Stanley.

13 recordsLinked to original sources

Viscous fingering of HCl through gastric mucin.

The HCl in the mammalian stomach is concentrated enough to digest the stomach itself, yet the gastric epithelium remains undamaged. One protective factor is gastric mucus, which forms a protective layer over the surface epithelium and acts as a diffusion barrier Bicarbonate ions secreted by the gastric epithelium are trapped in the mucus gel, establishing a gradient from pH 1-2 at the lumen to pH 6-7 at the cell surface. How does HCl, secreted at the base of gastric glands by parietal cells, traverse the mucus layer without acidifying it? Here we demonstrate that injection of HCl through solutions of pig gastric mucin produces viscous fingering patterns dependent on pH, mucin concentration and acid flow rate. Above pH 4, discrete fingers are observed, whereas below pH 4, HCl neither penetrates the mucin solution nor forms fingers. Our in vitro results suggest that HCl secreted by the gastric gland can penetrate the mucus gel layer (pH 5-7) through narrow fingers, whereas HCl in the lumen (pH 2) is prevented from diffusing back to the epithelium by the high viscosity of gastric mucus gel on the luminal side.

Animals

Long-range correlations in nucleotide sequences.

DNA sequences have been analysed using models, such as an n-step Markov chain, that incorporate the possibility of short-range nucleotide correlations. We propose here a method for studying the stochastic properties of nucleotide sequences by constructing a 1:1 map of the nucleotide sequence onto a walk, which we term a 'DNA walk'. We then use the mapping to provide a quantitative measure of the correlation between nucleotides over long distances along the DNA chain. Thus we uncover in the nucleotide sequence a remarkably long-range power law correlation that implies a new scale-invariant property of DNA. We find such long-range correlations in intron-containing genes and in nontranscribed regulatory DNA sequences, but not in complementary DNA sequences or intron-less genes.

Animals

Effect of viscosity on neurite outgrowth and fractal dimension.

The growth mechanism by which neurons achieve their characteristic ramified morphology has long been of interest, but determining whether physical parameters, such as viscosity, are important has been difficult due to a lack of useful hypotheses and standard reproducible techniques. We have recently shown that neurons exhibit fractal behavior and that their fractal dimension (df) is consistent with a physical process called diffusion-limited aggregation (DLA). We suggested that this DLA behavior might stem from viscosity differences, chemical gradients or electrical fields (Caserta et al., Phys. Rev. Lett., 64 (1990) 95-98). DLA is a model for a large family of growth processes. In order for a process to fit the DLA model, the growth rate must be proportional to the gradient of a field at a point on the growing structure (Feder, Plenum, New York, 1988, Ch. 4). Chemical, electrical, or fluid pressure fields can fit the model depending on the particular physical system under study. Here, we studied growth of retinal neurons from chick embryos in culture media of various fluid viscosities. Thus, we test whether DLA in this system was based on a fluid pressure field. As viscosity was increased from 1 to 4.3 cps, the number of neurite branches decreased 98%. However, there was no effect on df. Over this range of viscosities, total cellular protein synthesis decreased only 17%. The results indicate that, while differences in viscosity between the interior and exterior of the cell affect neurite outgrowth, they do not affect the fractal behavior of neurons. Thus, viscosity differences are not the basis for the DLA pattern of neuronal arborization.

Algorithms

A binding site model of membrane transport: binary and cooperative flows.

The flows of solute molecules in a membrane under the influence of concentration gradients are considered within the framework of classical physical theories. A lattice model is constructed in which the binding sites represent potential minima and the flows are regarded as a result of molecules' making discrete transitions between the binding sites. Expressions for two-component currents are derived from certain descriptions for the transition mechanism. Where the molecular movement is given the crudest description, permeability coefficients are identical for both components and there is no current coupling. Where the molecular movement is given some finer detail, the permeability coefficients differ and positive coupling of flows appears. Our result applies to a combination of flows of tracer and abundant species as well as, more generally, to any combination of flows of two components which are distinguishable yet kinetically similar. Also considered are binary currents whose transport mechanism is further controlled by allosteric cooperativity. Whether the cooperative control is short or long ranged, permeability coefficients and fluxes differ appreciably from those without cooperative control. Thus, unlike in the case of channel flow, current coupling here may be either positive or negative, depending on the strength and nature of cooperative coupling. Numerical evidence suggests that the permeability and coupling may have discontinuous behavior, possibly indicating the existence of phase transitions. Our lattice model, from which the formulations for the flows are obtained, is compatible with current concepts of membrane structure.

Binding Sites

Raman spectroscopy: a structural probe of glycosaminoglycans.

We report the first Raman spectroscopic study of the glycosaminoglycans chondroitin 4-sulfate, chondroitin 6-sulfate and hyaluronic acid, both in solution and in the solid state. To aid in spectral identification, infrared spectra were also recorded from films of these samples. Vibrational frequencies for important functional groups like the sulfate groups, glycosidic linkages, C-OH and the N-acetyl group can be identified from the Raman spectra. Certain differences in the spectra of the different glycosaminoglycans can be interpreted in terms of the geometry of the various substituents, while other differences can be related to differences in chemical composition.

Glycosaminoglycans

Opsin structure probed by raman spectroscopy of photoreceptor membranes.

The first nonresonance Raman spectra of photoreceptor membranes are presented. Information about the membrane protein, opsin, and the membrane phospholipids can be deduced. Opsin appears to contain alpha-helical structure but little beta structure. The tyrosine residues are predominantly hydrogen bonded, and disulfide bonds, if they are present, are not in the normal gauche-gauche configuration.

Animals

Laser raman spectroscopy--new probe of myosin substructure.

Laser Raman spectroscopy is used to probe the heterogeneous substructure of the large contractile protein myosin. Some peaks are assigned to specific chemical groups of the molecule; others, notably the conformationally sensitive amide III vibrations, provide information on the structurally distinct regions of the molecule. Deuteration of the NH groups is instrumental in the assignment of these vibrational modes. The relative intensities of bands typical of alpha-helical conformations (near 1265 and 1304 cm-1) and bands associated with nonhelical structure (near 1244 cm-1) are sensitive indicators of myosin substructure and represent potentially useful probes of conformational changes.

Animals

Models of ionic transport in biological membranes. Raman spectroscopy as a probe of valinomycin, gramicidin A', and rhodopsin conformations.

There is evidence that membrane proteins can serve as the functional units of ionic transport in biological membranes. Laser Raman spectroscopy has been used to probe specific molecular interactions inside two models of transport membrane proteins, valinomycin and gramicidin A. Conformational changes of these molecules, as well as specific interactions with ions, can be detected and may help elucidate how membrane transport proteins such as Na+ minus K+ ATPase and rhodopsin function. Resonance Raman spectroscopy has also been used to study conformational changes and protein-chromophore interactions in rhodopsin, the membrane protein that acts as the primary unit of visual excitation in the eye.

Adenosine Triphosphatases