PubMed Health⌕ Search

Biomedical subjects

Fredric M Menger

Publications and source records attributed to Fredric M Menger.

At least 19 recordsLinked to original sources
PubMed2006

Sodium ion internalized within phospholipid membranes.

Seven phospholipids, modified with ester groups in their hydrophobic chains, were synthesized and examined for their ability to promote sodium ion flux across vesicular membranes. It was found by 23Na NMR that only the phospholipids having short chain segments beyond their terminal ester groups catalyze sodium ion transfer by up to 2 orders of magnitude relative to a conventional phospholipid, POPC. The rates increase with the concentration of the ester-phospholipid admixed with POPC in the bilayer. More surprisingly, the rates increase with the time allowed for the vesicles to age. This was attributed to ester-phospholipid migrating in the bilayers to form domains that solubilize the sodium ion within the hydrocarbon interior of the membrane. Such membrane domains explain why shift reagent-modified NMR spectra display three 23Na signals representing sodium outside the vesicles, sodium within the vesicular water pools, and sodium within the membranes themselves.

Ion Transport↗
PubMed2006

Exposure of self-assembly interiors to external elements. A kinetic approach.

Five cationic surfactants, each bearing a single sulfur at various locations along their chains, were adsorbed into sodium dodecyl sulfate micelles. An oxidant, periodate, was added to the system, and the subsequent rate of thioether oxidation to sulfoxide, determined by NMR, was found to be diminished (more or less equally for all sulfur loci) by 2 orders of magnitude. In contrast, rates of hydrogen peroxide oxidation were hardly perturbed by micellization. Once again, however, there was no rate dependence on sulfur location within the chains. These results are interpreted in terms of a disordered micelle in which all chain positions have roughly equivalent access to the micelle surface. The kinetic method for assessing exposure to the external medium is applicable to self-assemblies and polymer systems wherever the NMR resolution so permits.

Kinetics↗
PubMed2006

A non-steroidal facial amphiphile.

This paper gives the synthesis of an unusual non-steroidal amphiphile consisting of a large rigid molecule that possesses two water-solubilizing sulfates on one face and an extended hydrophobic surface on the other. The properties of this compound have been examined by X-ray analysis, light and cryo-electron microscopy, surface tension, conductivity, microrheology, and NMR. Aqueous solutions behave quite differently from those of a conventional amphiphile with long linear and flexible chains (e.g., sodium dodecyl sulfate). Thus, there is evidence that the facial amphiphile self-assembles to form viscous networks, but without the traditional critical micelle concentration, as if assembly is a stepwise process. Emulsions of toluene in water promoted by the facial amphiphile are stable for many months. In contrast to conventional surfactants, the NMR peaks are obliterated in aqueous solutions of the facial amphiphile. Both X-ray and cryo-HRSEM data suggest a lamellar morphology.

Anthracenes↗
PubMed2006

Polymer-induced flip-flop in biomembranes.

This Account describes the ability of amphiphilic polymers (e.g., EO/PO/EO block copolymers) and polycations [e.g., quaternized poly(4-vinylpyridine)] to accelerate translocation from the inside leaflet to the outside leaflet ("flip-flop") within vesicle bilayer membranes. Driving forces and mechanisms of flip-flop catalyzed by the nonionic and cationic polymers are different. The nonionics are bound to the biological membrane via incorporation of their hydrophobic blocks into the inner part of the lipid bilayer occupied by the hydrocarbon chains. The resulting scrambling of lipid molecules is favored by the overall hydrophobicity of the copolymer and the volume of its hydrophobic block. External binding of the cationic polymers, on the other hand, is driven by electrostatic interactions between the positively charged polymer units and the negatively charged lipid headgroups within the outside leaflet. Electrostatic binding favors both the flip-flop of anionic lipid from the inner to outer leaflet and the formation of anionic domains in the outer leaflet. When it is considered that less than 1% of the liposome surface is occupied by certain bound polymers, their effect upon membrane dynamics, as will be described herein, is considerable. A distinct correlation has been found between the "flippase" activity of the polymers and their ability to mediate drug permeation through biomembranes.

Catalysis↗
PubMed2005

Peptoads, a group of amphiphilic long-chain triamides.

Eleven triamides bearing long alkyl chains have been synthesized to produce a new class of amphiphilic compounds (dubbed "peptoad"). The properties of these molecules have been investigated by X-ray analysis, solubility studies, light and electron microscopy, surface tensiometry, light scattering, drug dissolution, and molecular dynamics. In the solid state, the peptoads assemble in layers with both intra- and interlayer hydrogen bonding coupled to side-by-side proximity of the hydrocarbon chains. Peptoads with a terminal primary amide and a total of three amide NH sites are water-insoluble owing presumably to attractive forces in the solid state. However, peptoads with terminal -CONMe(2) groups and two internal amide NH sites are water-soluble at room temperature. This solubility is critically dependent upon the chain length. For example, a C(7)-chained peptoad is 1600 times more soluble than its C(9) analogue. High concentrations (6-8 M) of C(7) peptoads in water are clear and do not gel. Light microscopy shows long fibers floating in an isotropic liquid. Water-soluble peptoads are highly surface-active, lowering water's surface tension as effectively as a soap with a much longer chain. Surface tension plots show a "critical aggregation concentration", but it is believed from light scattering and molecular dynamics that the aggregates grow continuously as more peptoad is added to the water. In answer to the inevitable (but valid) question, "What possible good are they?", it can be pointed out that a peptoad solubilizes a water-insoluble drug, paclitaxel (Taxol), as efficiently as does Cremophor EL, a commercial excipient widely used with paclitaxel and other nonpolar drugs. Peptoads, being small molecules and consisting of hydrolyzable amide groups, are likely biodegradable and less prone to the hypersensitivity and neurotoxicity found with Cremophor EL.

Amides↗
PubMed2005

Surface tension of aqueous amphiphiles.

Surface tension measurements show that at low concentrations a surfactant bearing two ester groups in its chain assembles into small aggregates or else rearranges at the air/water interface to occupy less area per molecule. Only at higher surfactant concentrations do bona fide micelles form. The air/water interface, it is argued, saturates abruptly and cooperatively (as does the aggregation into micelles at the higher concentrations) to give a "critical monolayer concentration". Yet saturation does not reduce the surface tension a great deal. The bulk of surface tension reduction is imparted by monomeric surfactant in the solution via a mechanism that is obscure but may be related in part to the mechanical perturbation of the saturated film during measurement.

Adsorption↗
PubMed2005

Characterizing the "shell phase" formed from amphiphilic picolinates.

The shell phase forms when certain picolinates are subjected to energy input (via sonication or vortexing) while exposed to a water/toluene mixture. A shell, about 600 A thick and containing the picolinate and (very likely) toluene, surround the water droplets that are always produced during the mixing process. Solubility in either phase appears to be deleterious to shell formation. The shells, stable for months, are not easily distorted but can be punctured, even skewered, with a syringe needle without destroying the sphere, yet there is enough mobility among the molecules to repair the physical damage after the needle is removed. This, plus the absence of evidence for crystallinity, suggests a solid or semisolid film forms when picolinates, with the aid of an aromatic solvent, are provided the energy to rearrange themselves on water droplet surfaces. Structure-activity comparisons among the 10 compounds studied indicate that chain-chain association and intermolecular hydrogen bonding are dominant forces in a side-by-side self-assembly of the molecules within the shells.

Anesthetics, Local↗
PubMed2005

Is the ether group hydrophilic or hydrophobic?

A series of six surfactants, each with two ether oxygens within otherwise all-hydrocarbon chains, were synthesized and examined for their colloidal properties. Since an ether oxygen is sterically and conformationally similar to the methylene group it has replaced, the ether effect on micellization should stem mainly from solvation of the oxygen and, possibly, disrupted hydrophobicity of its adjacent carbons. It was found that critical aggregation values among the surfactants differ only modestly despite the total length of the ether-separated carbon segments ranging from 12 to 18. Shorter ether surfactants with only 12 or 14 total carbons appear to form small, loose aggregates owing, presumably, to a mild hydrophilicity of the ether groups. A surfactant with 18 chain carbons has a greater tendency to associate hydrophobically, but this is counterbalanced by a relatively water-free environment encountered by the ether groups within a more conventional micelle interior. The result is a leveling effect in which the critical aggregation concentration (cac) loses it sensitivity to chain length. Above their cac's, none of the ether surfactants is a good solubilizer of tetramethysilane or mesitylene. This is not necessarily a predictable finding since it was conceivable that the presence of interior ether groups might actually enhance solubilization (much as ether is a better solvent than hexane). Foamability and solid adsorption studies also indicate that the ethers impair surface activity. In response to the question posed in the paper's title, two ether groups are not sufficiently hydrophilic to prevent aggregation, but they do manage to alter the micelles' morphology and properties considerably.

Ethers↗
PubMed2004

Contiguous versus segmented hydrophobicity in micellar systems.

This paper addresses a question not yet posed systematically in surfactant chemistry: How do the colloidal properties of surfactants respond to insertion of non-hydrocarbon functionalities (i.e., ester groups) within chains that are normally entirely hydrocarbon? In answering this question, two classes of such chain-modified surfactants were discovered. One class forms only small aggregates with noncooperative self-assembly, low foaming, high areas of occupancy at the air/water interface, and weak solid-adsorption and solubilization properties. The other class is much more normal with regard to these properties and, in fact, can even exceed conventional surfactants in mesitylene solubilization. Differences between the two categories of chain-modified surfactants originate from the degree of segmentation of the hydrocarbon and, in particular, upon the location of the longest segment. Segmented hydrophobicity, having in principle a "hydrophobic potential" similar to that of a contiguous hydrophobicity of equal length, can induce aggregation but, concurrently, alters the mode of assembly into films and micelles.

Journal Article↗
PubMed2004

Membrane-bound protein in giant vesicles: induced contraction and growth.

Cell-sized giant vesicles, produced by electroformation, were composed of phospholipids and zein (a hydrophobic protein that occupied a substantial percentage of the vesicle surface). Addition of sodium dodecyl sulfate removed the protein into the bulk phase, which led to a shrinkage of the vesicles. The vesicle bilayers were able to heal themselves from the damage caused by the departure of the zein, allowing the bilayers to maintain their spherical morphology. Giant vesicle growth was also observed when the following components were mixed (all four being necessary): (a) negatively charged giant vesicles, (b) membrane-incorporated zein, (c) positively charged submicroscopic vesicles (almost 103 times smaller than the giant vesicles), and (d) sodium dodecyl sulfate. The simplest mechanism consistent with literature data involves electrostatically promoted binding of the small vesicles (weakened by the surfactant) onto the giant vesicle surface, followed by the merging of membranes at protein-induced "fusion hot spots". The "feeding" of small vesicles by giant vesicles then leads to growth.

Cell Membrane↗
PubMed2004

Ultrastructure in frozen/etched saline solutions: on the internal cleansing of ice.

Seawater, with its 3.5% salt content, freezes into hexagonal ice (Ih) that encloses concentrated brine within its matrix. When unsubmerged sea ice reaches a certain height and temperature, the brine drains downward through narrow channels. This mechanism was now modeled by frozen 2-3.5% saline as investigated by cryo-etch high-resolution secondary electron microscopy. Thus, saline was either plunge-frozen in liquid ethane at -183 degrees C or else high-pressure frozen to -105 degrees C in 5-6 ms. Ice from a freshly exposed surface was then subjected to a high-vacuum sublimation ("etching"), a procedure that removes pure bulk ice in preference to ice from frozen hydrated salt. After chromium-coating the etched surface with a 2-nm film, the sample was examined by cryo-HRSEM. Granular icy "fences" were seen surrounding empty areas where amorphous ice had originally resided. Since the fences, about 1-2 mum high, survived the etching, it is likely that they consist of frozen brine. The presence of such fences suggests that, during freezing, saline can purge itself of salt with remarkable speed (5-6 ms). Alternatively, channels (perhaps routed around submicroscopic crystallites of cubic ice (Ic) embedded in the amorphous ice at -105 degrees C) can guide the migration of salt to the periphery of ice patches. Macromolecules fail to form fences because they diffuse too slowly or because they are too large to pass through the channels.

Freeze Etching↗
PubMed2004

Vesicular latex.

Explore the source record for details and available documents.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2004

Bolaforms with fourteen galactose units: a proposed site-directed cohesion of cancer cells.

[structure: see text] The multistep synthesis of a calixarene joined to a second calixarene via a long spacer is described. Since each calixarene bears multiple galactose-based units (known to bind strongly to rat hepatoma cells), there existed the possibility of cross-linking the cancer cells into a network. The compounds did not serve this purpose, a fact potentially correctable by adjusting or rigidifying the spacer. Formation of a "cancer net" around a solid tumor remains a viable approach to retarding growth and/or inhibiting metastasis.

Animals↗
PubMed2003

Sugar/steroid/sugar conjugates: sensitivity of lipid binding to sugar structure.

[structure: see text]. Three steroids, each bearing a sugar on rings A and D, have been synthesized. Their effect on the "melting" behavior of a lipid bilayer depends on whether the sugar is glucose, galactose, or mannose. Packing constraints dictate how the lipid bilayer responds to the sugars.

1,2-Dipalmitoylphosphatidylcholine↗