Biomedical subjects

Srinivasa R Raghavan

Publications and source records attributed to Srinivasa R Raghavan.

16 recordsLinked to original sources

PubMed2007

Contrasting effects of temperature on the rheology of normal and reverse wormlike micelles.

Wormlike micelles are flexible polymerlike chains formed by the self-assembly of amphiphilic molecules either in water ("normal" worms) or in oil ("reverse" worms). Normal and reverse worms have both been studied extensively and have generally been found to exhibit analogous rheological properties (e.g., Maxwell fluidlike behavior). Here, we report a hitherto unexplored difference between these two classes of micelles pertaining to the effect of temperature on their rheological properties. For normal worms, the plateau modulus remains constant as the sample is heated while the relaxation time exponentially decreases. For reverse worms, however, both the plateau modulus and the relaxation time decrease exponentially upon heating. Consequently, the zero-shear viscosity of reverse worms decreases more rapidly with temperature than for normal worms. To explain these differences, we propose that increasing the temperature weakens the driving force for micellization in reverse worms whereas it only accelerates the dynamics of surfactant exchange in normal worms.

Journal Article↗

PubMed2007

Reversible vesicle restraint in response to spatiotemporally controlled electrical signals: a bridge between electrical and chemical signaling modes.

Microelectronic devices employ electrons for signaling whereas the nervous system signals using ions and chemicals. Bridging these signaling differences would benefit applications that range from biosensing to neuroprosthetics. Here, we report the use of localized electrical signals to perform an operation common to chemical signaling in the nervous system. Specifically, we employ electrical signals to restrain vesicles reversibly. We perform this operation using the stimuli-responsive aminopolysaccharide chitosan that is able to electrodeposit onto cathode surfaces in response to localized electrical stimuli. We show that surfactant-vesicles and liposomes can be co-deposited with chitosan and are entrapped (i.e., restrained) within the deposited film's matrix. Vesicle co-deposition could be controlled spatially and temporally using microfabricated wafers with independent electrode addresses. Finally, we show that vesicles restrained within the deposited chitosan matrix can be mobilized under mildly acidic conditions (pH <6.5) that resolubilize chitosan. Potentially, the ability to restrain and mobilize chemical signals that are segregated within vesicles may allow microfluidic systems to access the rich diversity offered by chemical signaling.

Animals↗

PubMed2006

Distinct kinetic pathways generate organogel networks with contrasting fractality and thixotropic properties.

The kinetics of the isothermal transformation of sols, comprised of a low molecular-mass organogelator (LMOG) and an organic liquid, to their organogel phases have been followed by circular dichroism (CD), fluorescence, small angle neutron scattering (SANS), and rheological methods. The thixotropic properties (in the sense that severe shearing followed by rest lead to reestablishment of viscoelasticity) of the gels have been examined as well by rheological measurements. The compositions of the samples were either 5alpha-cholestan-3beta-yl N-(2-naphthyl) carbamate (CNC) in an n-alkane (n-octane or n-dodecane) or 3beta-cholesteryl N-(2-naphthyl) carbamate (CeNC) in ethyl acetate. Values of Df, the mass fractal dimension of the microcrystalline self-assembled fibrillar networks (SAFINs) in the gels, have been extracted from the kinetic data using a model developed by Dickinson (J. Chem. Soc., Faraday Trans. 1997, 93, 111). The Df values, 1.1-1.3 for the CeNC gels and 1.3-1.4 or 1.6-1.8 (depending on the temperature of incubation of the sol phase) for CNC gels, are consistent with the gel network structures observed by optical microscopy. In addition, comparison of the temperature dependence of both n (the Avrami component) and K (the Avrami "rate constant") for CeNC/ethyl acetate gelation with those reported previously for gelation of CNC/n-alkane sols demonstrate that the very small change of a single bond in CNC to a double bond in CeNC causes significant differences in their gelation abilities and gel properties. The rheological measurements on CNC/n-alkane gels with spherulitic SAFIN units, formed by incubation of their sols at < or =28 degrees C, indicate that they are thixotropic. Gels with the same chemical composition but formed by incubation of their sols at > or =30 degrees C, leading to fiberlike SAFIN units, remain liquidlike after shearing regardless of the periods they are at rest. The time-dependent viscoelastic properties of the gel networks are treated according to a stretched exponential model. The observations from these studies provide detailed insights into the mechanisms of formation of molecular organogel phases and demonstrate the extreme sensitivity of the SAFINs and viscoelastic properties of such organogels to slight modifications in LMOG structure or sample history.

Journal Article↗

PubMed2006

Highly efficient capture and long-term encapsulation of dye by catanionic surfactant vesicles.

Vesicles formed from the cationic surfactant, cetyltrimethylammonium tosylate (CTAT) and the anionic surfactant, sodium dodecylbenzenesulfonate (SDBS), were used to sequester the anionic dye carboxyfluorescein. Carboxyfluorescein was efficiently sequestered in CTAT-rich vesicles via two mechanisms: encapsulation in the inner water pool and electrostatic adsorption to the charged bilayer. The apparent encapsulation efficiency (22%) includes both encapsulated and adsorbed fractions. Entrapment of carboxyfluorescein by SDBS-rich vesicles was not observed. Results show the permeability of the catanionic membrane is an order of magnitude lower than that of phosphatidylcholine vesicles and the loading capacity is more than 10 times greater.

Benzenesulfonates↗

PubMed2006

Self-assembly of surfactant vesicles that transform into viscoelastic wormlike micelles upon heating.

Unilamellar vesicles are observed to form in aqueous solutions of the cationic surfactant, cetyl trimethylammonium bromide (CTAB), when 5-methyl salicylic acid (5mS) is added at slightly larger than equimolar concentrations. When these vesicles are heated above a critical temperature, they transform into long, flexible wormlike micelles. In this process, the solutions switch from low-viscosity, Newtonian fluids to viscoelastic, shear-thinning fluids having much larger zero-shear viscosities (e.g., 1000-fold higher). The onset temperature for this transition increases with the concentration of 5mS at a fixed CTAB content. Small-angle neutron scattering (SANS) measurements show that the phase transition from vesicles to micelles is a continuous one, with the vesicles and micelles coexisting over a narrow range of temperatures. The tunable vesicle-to-micelle transition and the concomitant viscosity increase upon heating may have utility in a range of areas, including microfluidics, controlled release, and tertiary oil recovery.

Cetrimonium↗

PubMed2006

A new reverse wormlike micellar system: mixtures of bile salt and lecithin in organic liquids.

We report a new route for forming reverse wormlike micelles (i.e., long, flexible micellar chains) in nonpolar organic liquids such as cyclohexane and n-decane. This route involves the addition of a bile salt (e.g., sodium deoxycholate) in trace amounts to solutions of the phospholipid lecithin. Previous recipes for reverse wormlike micelles have usually required the addition of water to induce reverse micellar growth; here, we show that bile salts, due to their unique "facially amphiphilic" structure, can play a role analogous to that of water and promote the longitudinal aggregation of lecithin molecules into reverse micellar chains. The formation of transient entangled networks of these reverse micelles transforms low-viscosity lecithin organosols into strongly viscoelastic fluids. The zero-shear viscosity increases by more than 5 orders of magnitude, and it is the molar ratio of bile salt to lecithin that controls the viscosity enhancement. The growth of reverse wormlike micelles is also confirmed by small-angle neutron scattering (SANS) experiments on these fluids.

Bile Acids and Salts↗

PubMed2006

Bioinspired vesicle restraint and mobilization using a biopolymer scaffold.

Biology employs vesicles to package molecules (e.g., neurotransmitters) for their targeted delivery in response to specific spatiotemporal stimuli. Biology is also capable of employing localized stimuli to exert an additional control on vesicle trafficking; intact vesicles can be restrained (or mobilized) by association with (or release from) a cytoskeletal scaffold. We mimic these capabilities by tethering vesicles to a biopolymer scaffold that can undergo (i) stimuli-responsive network formation (for vesicle restraint) and (ii) enzyme-catalyzed network cleavage (for vesicle mobilization). Specifically, we use the aminopolysaccharide chitosan as our scaffold and graft a small number of hydrophobic moieties onto its backbone. These grafted hydrophobes can insert into the bilayer to tether vesicles to the scaffold. Under acidic conditions, the vesicles are not restrained by the hydrophobically modified chitosan (hm-chitosan) because this scaffold is soluble. Increasing the pH to neutral or basic conditions allows chitosan to form interpolymer associations that yield a strong, insoluble restraining network. Enzymatic hydrolysis of this scaffold by chitosanase cleaves the network and mobilizes intact vesicles. Potentially, this approach will provide a controllable means to store and liberate vesicle-based reagents/therapeutics for microfluidic/medical applications.

Chitosan↗

PubMed2006

Transition from unilamellar to bilamellar vesicles induced by an amphiphilic biopolymer.

We report some unusual structural transitions upon the addition of an amphiphilic biopolymer to unilamellar surfactant vesicles. The polymer is a hydrophobically modified chitosan and it embeds its hydrophobes in vesicle bilayers. We study vesicle-polymer mixtures using small-angle neutron scattering (SANS) and cryotransmission electron microscopy (cryo-TEM). When low amounts of the polymer are added to unilamellar vesicles of ca. 120 nm diameter, the vesicle size decreases by about 50%. Upon further addition of polymer, lamellar peaks are observed in the SANS spectra at high scattering vectors. We show that these spectra correspond to a co-existence of unilamellar and bilamellar vesicles. The transition to bilamellar vesicles as well as the changes in unilamellar vesicle size are further confirmed by cryo-TEM. A mechanism for the polymer-induced transitions in vesicle morphology is proposed.

Chitosan↗

PubMed2005

Viscosity increase with temperature in cationic surfactant solutions due to the growth of wormlike micelles.

Wormlike micellar solutions based on ionic surfactants typically show an exponential decrease in viscosity upon heating. Here, we report the unusual observation of an increasing viscosity with temperature in certain cationic wormlike micellar solutions. The solutions contain a cationic surfactant with an erucyl (C22, mono-unsaturated) tail and an organic salt, sodium hydroxynaphthalene carboxylate (SHNC). When these solutions are heated, their zero-shear viscosity increases over a range of temperatures. In some cases, the viscosity reaches a peak at a certain temperature and then decreases with further heating. The magnitude of the viscosity increase, the onset of this increase, and the peak temperature can all be tuned by varying the SHNC concentration. Small-angle neutron scattering is used to study the origin of this unusual rheological behavior. The data reveal that the contour length of the micelles increases with temperature, in tandem with the rise in viscosity. A possible explanation for the contour length increase, based on a temperature-dependent counterion binding, is discussed.

Journal Article↗

PubMed2005

Salt effects on the phase behavior, structure, and rheology of chromonic liquid crystals.

Chromonic liquid crystals are formed by the addition of aromatic molecules such as disodium chromoglycate (cromolyn) to water. In this study, we investigate the addition of salts to the lyotropic nematic phase of cromolyn aqueous solutions. The addition of sodium and potassium salts shifts the isotropic-nematic phase boundary upward by more than 10 degrees C, so that samples that were isotropic at room temperature are transformed into nematic phases. Salt effects are predominantly dictated by the cation, not the anion, and appear to differ based on cation size. In contrast to small, hydrated cations like sodium, large, weakly hydrated cations such as tetraethylammonium and tetrabutylammonium shift the phase boundary downward, thus stabilizing the isotropic phase at the expense of the nematic one. The phase behavior results are highly correlated with viscosity measurements, with an upward shift in the phase boundary correlating with an increase in solution viscosity and vice versa. We also probe the microstructure in cromolyn-salt solutions, both indirectly by small-angle neutron scattering (SANS) and directly by cryo-transmission electron microscopy (cryo-TEM). The cryo-TEM images show the presence of rodlike aggregates that possibly undergo a higher order aggregation into bundles in the presence of salt.

Cromolyn Sodium↗

PubMed2005

Anionic wormlike micellar fluids that display cloud points: rheology and phase behavior.

We report our investigations into the self-assembly of sodium oleate (NaOA) in the presence of a binding salt (triethylammonium chloride, Et(3)NHCl) simple salt (potassium chloride, KCl). Both salts promote the growth of long, wormlike micelles in NaOA solutions, thereby increasing the fluid viscosity. The significant difference with the Et(3)NHCl salt is that it also modifies the phase behavior of NaOA solutions. Specifically, NaOA/Et(3)NHCl solutions display cloud points upon heating, followed by phase separation into two liquid phases. Such cloud point behavior is rarely observed in ionic surfactant systems, although it is common in nonionic surfactant solutions. Interestingly, while cloud points are not observed with KCl, the addition of KCl to NaOA/Et(3)NHCl solutions further lowers the cloud point temperature. Also, in the case of tetraethylammonium halide salt, neither a cloud point nor an increase in viscosity is observed. The clouding in the case of Et(3)NHCl is attributed to the temperature-induced aggregation of anionic micelles whose surface is covered by bound counterions.

Journal Article↗

PubMed2005

Kinetics of 5alpha-cholestan-3beta-yl N-(2-naphthyl)carbamate/n-alkane organogel formation and its influence on the fibrillar networks.

The kinetics and mode of nucleation and growth of fibers by 5alpha-cholestan-3beta-yl N-(2-naphthyl)carbamate (CNC), a low-molecular-mass organogelator (LMOG), in n-octane and n-dodecane have been investigated as their sols were transformed isothermally to organogels. The kinetics has been followed in detail by circular dichroism, fluorescence, small-angle neutron scattering, and rheological methods. When treated according to Avrami theory, kinetic data from the four methods are self-consistent and describe a gelation process involving one-dimensional growth and "instantaneous nucleation". As expected from this growth model, polarized optical micrographs of the self-assembled fibrillar networks (SAFINs) show fibrous aggregates. However, their size and appearance change abruptly from spherulitic to rodlike as temperature is increased. This morphological change is attended by corresponding excursions in static and kinetic CD, fluorescence and rheological data. Furthermore, the rheological measurements reveal an unusual linear increase in viscoelastic moduli in the initial stages of self-assembly. Each of the methods employed becomes sensitive to changes of the system at different stages of the transformation from single molecules of the LMOG to their eventual SAFINs. This study also provides a methodology for investigating aggregation phenomena of some other self-assembling systems, including those of biological and physiological importance.

Journal Article↗

PubMed2005

Vesicle--biopolymer gels: networks of surfactant vesicles connected by associating biopolymers.

The effect of adding an associating biopolymer to surfactant vesicles and micelles is studied using rheology and small-angle neutron scattering (SANS). The associating polymer is obtained by randomly tethering hydrophobic alkyl chains to the backbone of the polysaccharide, chitosan. Adding this polymer to surfactant vesicles results in a gel; that is, the sample transforms from a Newtonian liquid to an elastic solid having frequency-independent dynamic shear moduli. SANS shows that the vesicles remain intact within the gel. The results suggest a gel structure in which the vesicles are connected by polymer chains into a three-dimensional network. Vesicle-polymer binding is expected to occur via the insertion of polymer hydrophobes into the vesicle bilayer. Each vesicle thus acts as a multifunctional junction in the network structure. Significantly, gel formation does not occur with the native chitosan that has no hydrophobes. Moreover, adding the hydrophobically modified chitosan to a viscous sample containing wormlike micelles increases the viscosity further but does not give rise to a gel-like response. Thus, the formation of a robust gel network requires both the presence of hydrophobes on the polymer and vesicles in solution.

Journal Article↗

PubMed2005

Developing decision support for dialysis treatment of chronic kidney failure.

The complexity, variability, quantitative nature, and data density of treatment for chronic kidney failure make dialysis information systems excellent candidates for computerized decision support. We describe the development of an intelligent system building on existing knowledge and susceptible to reconfiguration on the basis of knowledge acquired during the use of the system. Various decision support techniques were used to design and develop the decision support modules. This paper briefly reviews the literature on clinical decision support, discusses some of the problems faced by practitioners in managing chronic kidney failure (end-stage renal disease) patients, and sets forth the decision support techniques used in developing a dialysis decision support system.

Anemia↗

PubMed2004

Shear-induced phase separation in solutions of wormlike micelles.

Polymer solutions in the vicinity of the theta-point are known to undergo shear-induced turbidity or phase separation. The present study shows that a similar phenomenon also occurs for certain wormlike micellar solutions. Wormlike micelles are the self-assembled counterparts of polymers and are characterized by their ability to reversibly break and recombine. In the system of interest, the micelles are formed by the cationic surfactant erucyl bis(hydroxyethyl)methylammonium chloride (EHAC), in conjunction with a salt such as sodium chloride (NaCl) or sodium salicylate (NaSal). Micellar samples that become turbid under shear show evidence of critical concentration fluctuations and may contain predominantly branched micelles. The shear-induced turbidity in these samples correlates with the appearance of flow-dichroism in rheooptic experiments and with an increase in low-q scattering in small-angle light scattering under flow (flow-SALS) experiments. The characteristic "butterfly" pattern, with enhanced scattering in the flow direction and a dark streak perpendicular to the flow direction, is typically observed in flow-SALS. The results suggest that the turbidity is due to a shear-induced growth of concentration fluctuations, which in turn manifests as large anisotropic domains, typically oriented along the vorticity axis.

Journal Article↗

PubMed2004

Enzymatic grafting of peptides from casein hydrolysate to chitosan. Potential for value-added byproducts from food-processing wastes.

Tyrosinase was used to initiate the grafting of peptides onto the amine-containing polysaccharide chitosan. Chemical evidence for covalent grafting was obtained from electrospray mass spectrometry for products formed from reactions with glucosamine (the monomeric unit of chitosan) and the model dipeptide Tyr-Ala. When this model dipeptide was incubated with tyrosinase and chitosan, there was a marked increase in the viscosity of the solution. This viscosity increase provides physical evidence that tyrosinase can initiate peptide grafting onto the chitosan backbone. A peptide-modified chitosan derivative was generated by reacting chitosan (0.32 w/v%) with acid-hydrolyzed casein (0.5 w/v %) using tyrosinase. After reaction, the peptide-modified chitosan was partially purified and dissolved in an aqueous acetic acid solution. Low concentrations of this peptide-modified chitosan were observed to confer viscoelastic properties to the solutions. Specifically they conferred high viscosities and shear thinning properties to the solutions, and solutions containing only 1 w/w % of the peptide-modified chitosan behaved as weak gels. Thus, tyrosinase provides a simple and safe way to convert food-processing byproducts into environmentally friendly products that offer useful functional properties. The selectivity of tyrosinase and the relatively high reactivity of chitosan's amines allow grafting to be performed with uncharacterized peptide mixtures present in crude hydrolysates.

Caseins↗