The physical chemistry of biological membranes

Physical chemistry explains the principles of self-organization of lipids into bilayers that form the matrix of biological membranes, and continuum theory of membrane energetics is successful in explaining many biological processes. With increasing sophistication of investigative tools, there is now a growing appreciation for lipid diversity and for the role of individual lipids and specific lipid-protein interactions in membrane structure and function.     

Structure and physical chemistry of membranes

Summary With the concept of the unit membrane as a central theme, a number of current problems for the theory of membrane structures are discussed from the point of view of the physical chemist. In view of the wide variety of chemical compositions of membranes, some current opinions of the forces maintaining the integrity of membranes are of limited generality. The thermodynamic status of the membrane is discussed, and it is suggested that the new small-systems thermodynamics can be usefully employed as a conceptual basis for discussing fluctuations and phase-changes in membranes. Arguments are given to suggest that the lipid interior of membranes is more ordered and crystalline than is currently supposed. The role of water in membrane structures remains an enigma.     

Variations in the intensity of solar neutrinos as a problem for physical chemistry

A comparison of variations in the solar neutrino flux in Brookhaven measurements with solar activity indices clearly shows that the neutrino flux is controlled by surface solar processes. These processes can lead to changes in the efficiency of registrations of the neutrino flux. From this view point, the results of the measurements of the neutrino flux on the Brookhaven detector in 1970-1994 (108 runs) were analyzed. It was found that the neutrino flux depends on the heliogeophysical situation. The well known anticorrelation between the neutrino flux and Wolf numbers is observed only for odd cycle of solar activity. A similar regularity occurs for critical frequencies of E-ionosphere. By contrast, the correlation between the neutrino flux and the Ap-index is observed only for the even activity cycle. The predominance of the sign of radial component of the interplanetary magnetic field in the last 7-14 days of exposure has the greatest effect on the neutrino flux (this sign changes as the sign of the total magnetic field of the Sun changes). In short runs, the neutrino flux changes more than threefold. The conclusion is made that variations of the solar neutrino flux are falcious. These fictitious variations are caused probably by the action of very low-frequency electromagnetic emissions of the magnetosphere upon the substance of the target and the technology of the extraction of 37Ar atoms from perchloretylene.     

The mechanical behaviour of cell membranes as a possible physical origin of cell polarity

The mechanical behaviour of a closed layered membrane enclosing a structureless interior is considered. The shape of such an object in flaccid conditions is determined theoretically by assuming that it corresponds to the minimum value of the membrane bending energy. The symmetry breaking properties of this system are revealed. It is suggested that a continuous transition from an axisymmetrical shape involving mirror symmetry with regard to the equatorial plane of the object to the shape with polar asymmetry could be the primary event in establishing cell polarity.     

The biological and physical chemistry of polyhydroxyalkanoates as seen by NMR spectroscopy

Abstract The use of ¹³C NMR spectroscopy to study the biosynthesis, degradation and physical properties of polyhydroxyallkanoates (PHAs) is described. Solution-state NMR of whole cells allows direct observation of biosynthetic pathways within the cell and demonstrates that the bulk of the polymer is in a remarkably fluid, amorphous state. A new model is proposed for the maintenance of this state in vivo: the known rate of crystal nucleation combined with the physical dimensions of the native PHA granule lead naturally to the conclusion that polymer morphology is under kinetic rather than thermodynamic control. Finally solid-state NMR studies of isolated PHAs allow observation of separate crystalline regions based on hydroxybutyrate and hydroxyvalerate and measurement of the HB and HV contents of these and amorphous domains.     

An actograph for small laboratory animals controlled by a personal computer

This system for measuring behavioral activity and for its analysis by personal computer as the recording device of the actograph was developed in order to measure the drinking activity and the feeding activity of small laboratory animals. According to the results of the measurement on male DBA/2J mice with this actograph, 84.0% of the drinking activity occurred in the dark period while 16.0% in the light period, and the amount of water drunk by the mouse was about 5.7 ml/day under the conditions of a 12 hour light period and 12 hour dark period. Under the same conditions, 79.6% of the feeding activity took place in the dark period and 20.4% in the light period. Also there was a positive correlation between both activities.     

The Golgi complex as a source for yeast autophagosomal membranes

Today, more than 50 years after the discovery of autophagy, the origin of the autophagosomal membranes remains for the most part elusive. Many sources for the lipid bilayers have been proposed, but no conclusive evidence has been found to support one particular origin. The lipids do not appear to be generated at the site of autophagosome formation, the phagophore assembly site (PAS), since so far no lipid synthesizing enzyme has been found at this location. The current consensus is also that the autophagosomes do not directly bud off from a pre-existing compartment, and recent evidence in mammalian cells has revealed that the nascent autophagosome could expand through a lipid transfer mechanism from an adjacent organelle. In yeast, such an event has never been observed and data from our and other laboratories suggest that the Golgi complex could be a key player in mediating the expansion of the phagophore.     

The physical state of quick-frozen membranes and lipids

Lipid bilayers and biomembranes produce nearly identical calorimeter scans regardless of whether they are slowly cooled under near-equilibrium conditions or rapidly frozen at rates used in freeze-fracture electron microscopy. Except for the melting of ice at 273 K, for both cooling regimens no significant thermal events occur from 100 K to the usual gel to liquid crystal transition. The gel to liquid crystal transition itself is somewhat altered by rapid cooling when bilayers contain mixed lipid species. Combined with X-ray diffraction studies, the results indicate that quickly frozen bilayers are crystalline, but that the crystalline domains are quite small or otherwise disordered. In contrast to the behavior of lipids in bilayers, hexagonal-phase calcium cardiolipid easily forms a glass upon cooling.     

The Nile grass rat as a laboratory animal

Rodents are the subjects of the overwhelming majority of laboratory animal studies, and most laboratory rodents are nocturnal. The availability of a suitable diurnal rodent would provide a more effective animal model for biomedical research applicable to humans. The author describes several characteristics of the Nile grass rat that make this diurnal murid rodent an attractive laboratory animal.     

The effect of ethanol on the physical properties of neuronal membranes

Intramolecular excimer formation of 1,3-di(1-pyrenyl) propane(Py-3-Py) and fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH) were used to evaluate the effect of ethanol on the rate and range of lateral and rotational mobilities of bulk bilayer structures of synaptosomal plasma membrane vesicles (SPMVs) from the bovine cerebral cortex. Ethanol increased the excimer to monomer fluorescence intensity ratio (I'/I) of Py-3-Py in the SPMVs. Selective quenching of both DPH and Py-3-Py by trinitrophenyl groups was used to examine the range of transbilayer asymmetric rotational mobility and the rate and range of transbilayer asymmetric lateral mobility of SPMVs. Ethanol increased the rotational and lateral mobility of the outer monolayer more than of the inner one. Thus ethanol has a selective fluidizing effect within the transbilayer domains of the SPMVs. Radiationless energy transfer from the tryptophans of membrane proteins to Py-3-Py was used to examine both the effect of ethanol on annular lipid fluidity and protein distribution in the SPMVs. Ethanol increased annular lipid fluidity and also caused membrane proteins to cluster. These effects on neuronal membranes may be responsible for some, though not all, of the general anesthetic actions of ethanol.     

A laboratory exercise using a physical model for demonstrating countercurrent heat exchange

A physical model was used in a laboratory exercise to teach students about countercurrent exchange mechanisms. Countercurrent exchange is the transport of heat or chemicals between fluids moving in opposite directions separated by a permeable barrier (such as blood within adjacent blood vessels flowing in opposite directions). Greater exchange of heat or chemicals between the fluids occurs when the flows are in opposite directions (countercurrent) than in the same direction (concurrent). When a vessel loops back on itself, countercurrent exchange can occur between the two arms of the loop, minimizing loss or uptake at the bend of the loop. Comprehension of the physical principles underlying countercurrent exchange helps students to understand how kidneys work and how modifications of a circulatory system can influence the movement of heat or chemicals to promote or minimize exchange and reinforces the concept that heat and chemicals move down their temperature or concentration gradients, respectively. One example of a well-documented countercurrent exchanger is the close arrangement of veins and arteries inside bird legs; therefore, the setup was arranged to mimic blood vessels inside a bird leg, using water flowing inside tubing as a physical proxy for blood flow within blood vessels.     

Drug Guru: a computer software program for drug design using medicinal chemistry rules

Drug Guru (drug generation using rules) is a new web-based computer software program for medicinal chemists that applies a set of transformations, that is, rules, to an input structure. The transformations correspond to medicinal chemistry design rules-of-thumb taken from the historical lore of drug discovery programs. The output of the program is a list of target analogs that can be evaluated for possible future synthesis. A discussion of the features of the program is followed by an example of the software applied to sildenafil (Viagra) in generating ideas for target analogs for phosphodiesterase inhibition. Comparison with other computer-assisted drug design software is given.