[Gelation in Low Concentrated Solutions of Cholesterol and Ergosterol].

The molecular dynamics method has been applied to investigate the conformational behavior of biologically important chiral molecules of cholesterol and ergosterol. The formation of strings in the solution of cholesterol in methanol and the lack of strings in solutions of ergosterol in methanol has been experimentally detected. It was shown that the intermolecular dynamics in the molecule has a significant impact on the potential of structure formation. We proposed alternative explanation of the functional significance of cholesterol, apparently associated with the formation of interconnect structures outside the membrane as the biological feasibility of finding ergosterol in non-switched cells of fungi and cholesterol in the switching cells of macroorganisms.

[Influence of Storage Temperature and Cryopreservation Conditions on the Extent of Human Sperm DNA Fragmentation].

With the direct labeling procedure for detecting DNA fragmentation we explored the influence of the different storage temperature conditions as well as different methods of cryopreservation on the structure of DNA organization in the human sperm. 19 sperm samples obtained from healthy men with normozoospermia (according to the criteria of the World Health Organization) were used for investigation. A significant increase of human sperm DNA-fragmentation was observed after 8 hours of incubation at +39 degrees C (by 76.7%) and at +37 degrees C (by 68.9%). It was found that sperm cooling with the use of a cryoprotectant immediately after thawing did not produce significant differences in the extent of DNA fragmentation, although samples, containing cryoprotectants, showed a sharp increase of DNA fragmentation after 24 hours of incubation, that could suggest cryoprotectant cytotoxicity.

["Microbiological aging" by Mechnikov. How to interpret these ideas today?].

I.I. Mechnikov's hypothesis that the key to prolongation of life lies in the introduction of useful microflora to the gut was not proved. Any microflora needs nutrition and perceives the human body only as a nutrient substrate. Destruction of the basement membranes, that delimit the contacting with aggressive microbiological environment epithelium from the deeper parts of the body, can lead to chronic inflammatory diseases and aging of the skin as a consequence of the invasion of microorganisms. At the ultrastructural level it has been shown by the example of prostatitis and skin aging changes. Coupled with the penetration of germs flow of immune cells may cause autoimmune reactions due to abrupt changes in the molecular design of the intermembrane transport. Thus, the physiological process of macroorganism aging can be viewed as a consequence of its microbiological destruction.

[Experimental observation of synergetic regular change of chirality sign in the hierarchy of biomimetic structures].

Having investigated chiroptical characteristics of homochiral solutions of biomimetics the rule of changing a chirality sign in spontaneous formation of supramolecular helical structures was experimentally substantiated. This self-organization presents evidence of a fundamental synergetic law of changing the chirality sign during the transition to a higher hierarchical level, being of common for modular prebiotic homochiral systems and basic molecular biological systems.

[Chirality as a primary switch of hierarchical levels in molecular biological systems].

A synergetic law, being of common physicochemical and biological sense, is formulated: any evolving system that possesses an excess of free energy and elements with chiral asymmetry, while being within one hierarchical level, is able to change the type of symmetry in the process of self-organization increasing its complexity but preserving the sign of a prevailing chirality (left - L or right - D twist). The same system tends to form spontaneously a sequence of hierarchical levels with alternating chirality signs of de novo formed structures and with an increase of the structures relative scales. In living systems, the hierarchy of conjugated levels of macromolecular structures that begins from the "lowest" asymmetric carbon serves as an anti-entropic factor as well as the structural basis of "selected mechanical degrees of freedom" in molecular machines. During transition of DNA to a higher level of structural and functional organization regular alterations of the chirality sign D-L-D-L and L-D-L-D for DNA and protein structures, respectively, are observed. Sign-alternating chiral hierarchies of DNA and protein structure, in turn, form a complementary conjugated chiral pair that represents an achiral invariant, that "consummates" the molecular-biological block of living systems. The ability of a carbon atom to form choral compounds is an important factor that determined carbon basis of living systems on the Earth as well as their development though a series of chiral bifurcations. The hierarchy of macromolecular structures demarcated by the chirality sign predetermined the possibility of the "block" character of biological evolution.

Metric similarity of dynamic commutation processes in situ and in vitro.

The dynamics of string growth was studied in model homochiral solutions of biomimetics, trifluoroacetylated amino alcohols (TFAAA) in heptane, water, and inverted heptane-water emulsion. In heptane and water, a thick (~1 µ in diameter) string had a crown of thin strings on its growing terminal and these thin strings effectively adsorbed dissolved TFAAA. In emulsion, the strings grew inside the water droplets, in which this TFAAA cannot be solved, presumably due to transport of TFAAA molecules from heptane into water in the surface layer surrounding the string. Applications of these phenomena to in vivo cell commutation were discussed.

Biological fluids as chiral anisometric media.

Molecules of dissolved substance in many homochiral solutions are arranged in linear associations forming chiral strings (with length to diameter proportion of 10(1)-10(5)), which leads to solidification of the solution into anisometric gel. This paper describes the formation of the string system in aqueous solution of amino acid phenylalanine, formation of individual strings, weaving of thin strings into thick ones, successive alteration of the solution chirality sign with transition to new levels of the association organization. It seems that biological media are anisometric fluids containing chiral molecular associations and strings, or anisometric gels.

[From symmetries to the laws of evolution. I. Chirality as a means of active media stratification].

Features of the hypothetical evolution of a hierarchy of chiral objects formed by active media are discussed. On the basis of experimental facts a new synergetic generalization is made: an evolving system can repeatedly broaden the spectrum of its symmetry types within one level of organization which increases its complexity and change the sign of chirality during transition to a higher level. Switching the chirality sign of macroscopic objects provides irreversibility of stratification. The known chirality of biological structures at different levels suggests that the chiral L/D-stratification should be universal and the hierarchical paths are stable and determined. A high level enantiomorph with reciprocal chirality demonstrates a wider spectrum of functionality. A fractal description of natural hierarchical systems is pointed out to be inadequate because it implicates invariance of the chirality sign of the objects at different scales.

Superspiralization of chiral strings.

A phenomenon of superspiralization was revealed in homochiral solutions of biomimetics with strings lengths from 10(2) nm to 10(2) µ and longer: strings of greater size spontaneously formed in solution are twined of the smaller strings, which also have a helical structure. The chiral pitch depends on the conditions of formation of a particular string and can vary by several times in different strings of the same specimen.

[Native and chiral modified NMDA-receptor NR1-binding core ligands modeling].

Native and chiral modified (with non-enzymatic Asn racemization) NR1-binding core of NMDA-receptor was modelled by means of molecular dynamic ligand modelling. It was concluded that Gly, D-Ser, D-Asn and D-Thr are ligands of NR1-binding core native NMDA-receptor, whereas the chiral modified NR1-binding core is characterized by the aliphatic non-polar amino acids D-Ala, D-Leu, D-Ile and D-Pro as ligands. The latter amino acids can be considered as effective ligands of NMDA-receptor NR1-binding core in age-related pathology.

[Energy distribution and ionic selectivity of the bacterial potassium channel].

An explanation for the ionic selectivity of the bacterial potassium channel K(CS)A is offered, which is based on a comparison of energy interactions of lithium, sodium, and potassium cations with the atoms of the selective filter of an protein pore. Using quantum-chemical calculations, the presence of a deeper potential hole for potassium ions was discovered, which explains the energy preferableness in their permeability. It has been shown that the traditional methods of force field AMBER, CHARMM, OPLS in reference parametrization and also at their partial reparametrization give incorrect ratings of energy distribution of ions in the channel.

[Mixed monolayers of amphiphile-modified nucleic bases and diynoic acids. I. Phase states at air-water interface and in Langmuir-Blodgett films]. / Smeshannye monosloi amfifil'nykh proizvodnykh azotistykh osnovanii i diinovykh kislot. I. Fazovoe sostoianie na granitse voda-vozdukh i v plenkakh Lengmiura-Blodzhett.

Monolayers of amphiphile-modified nucleic bases with diynoic acid were obtained and characterized. The synthesized nucleic bases contained in the monolayer complementarily bind the nucleotide molecules contained in the aqueous subphase, and the structure of the resulting monolayers can be fixed by the photopolymerization of diynoic acid. The resulting monolayer exemplifies a novel type of model systems for investigating molecular recognition at the surface of biological membranes. Procedures for the transfer of the monolayers onto solid substrates and photopolymerization of the diynoic acid in mixtures with the derivatives of nucleic bases were developed. The films obtained were structurally characterized using atomic force microscopy. Compression isotherms of the mixed monolayers as well as individual components of monolayers at the air-water interface allowed one to determine the concentration range at which the diynoic acid form true mixtures or domain structures with the derivatives of nucleic base. A study of the films transferred to the solid substrate by atomic force microscopy indicated that this concentration dependence of miscibility behavior was conserved in the transferred films.

[The school of Blumenfeld today]. / Shkola Bliumenfel'da segodnia.

A historical survey of the activity of the Chair of Biophysics of the Physical Faculty of the Moscow State University as a scientific school of L.A. Blumenfeld, its founder and head, is given. The principles of training the students in specialty "Biochemical physics" are described, and the main lines of research that are being currently developed at the chair are listed.

[On the methods of calculation of the electrostatic potential in a protein channel]. / O metoda rascheta raspredeleniia potentsiala v belkovom kanale.

The profiles of the electrostatic potential along the axis of a gramicidin channel were calculated using two quantum chemistry methods (EHT and CNDO/2) and three methods of force fields (AMBER, CHARMM, and OPLS). The calculations were performed without taking into account the contribution of water. A comparative analysis of the calculated profiles indicated that the electrostatic field of point charges of the CHARMM force field is close to that obtained by the quantum chemistry methods. It was concluded that there is no need to calculate the electric field using laborious quantum-mechanical methods since the less laborious method of the CHARMM force field gives approximately the same results.

[Chiral safety of the biosphere as a biophysical problem]. / Khiral'naia bezopastnost' biosfery kak biofizicheskaia problema.

The biosphere with its inherent chiral asymmetry fixed in the process of biological evolution at the level of L-amino acids and D-hydrocarbons and some other biologically active compounds of biogenic origin is under strong pressure of chiral substances produced by chemical, pharmaceutical, and other branches of industry and agriculture. Effective use of enantiomers is accompanied by toxic and even mutagenic effects of their mirror-image enantiomorphs. Only small amounts of products are tested for chiral purity; there is no system of global biosphere monitoring as well as no common standards of permissible concenrations. The investigation of the molecular basis of chiral stereospecificity of enzymes and cell receptors is of great interest from the point of view of fundamental biophysics. On the other hand, the development of chiral-selective sensors for environmental monitoring is important from the viewpoint of applied biophysics.

[Permeabilization of cell membrane by programmed form of electrical pulses]. / Permeabilizatsiia kletochnykh membran élektricheskimi impul'sami programmiruemoi formy.

The role of the shape of electric pulses of cell permeabilization and lysis was studied using the newly developed DPS electroporator. The effects of bipolar pulses, steep rising and falling edges in the pulses, delays between pulses, and shapes of DC signals between the edges on the lysis of bovine oocytes and the permeabilization of their cell membranes were investigated. Comparing the permeabilization rates with the lysis rates revealed a number of correlations, which make it possible to optimize the pulse shapes for achieving maximum permeabilization rates while keeping the lysis rates low. The optimization of pulse shape is essential for improving the procedure of electroporation in mammalian cloning technology.

[Surface of the Pacific Ocean and physical mechanisms of prebiological evolution]. / Poverkhnost' mirovogo okeana i fizicheskie mekhanizmy predbiologicheskoi évoliutsii.

The hypothesis about the spontaneous generation of living cell predecessors on the ocean surface during prebiological evolution is further developed. Data obtained in experiments and observations are given that support our point of view. It is shown that the physicochemical properties of the nonequilibrium ocean-atmosphere boundary including ionic asymmetry, fractionation of enantiomers of amino and nucleic acids, and the formation of sealed vesicles provide conditions under which the spontaneous generation seems quite possible.

Role of lipid membrane-nucleic acid interactions, DNA-membrane contacts and metal (II) cations in origination of initial cells and in evolution of prokaryotes to eukaryotes.

The problems of the origin of primary cells and eukaryotic cells are discussed in terms of possible role of interactions between nucleic acids with lipid membrane according to corresponding original hypothesis. We propose that there are two main hypotheses of the origin of primary cells: (a). RNA appeared before proteins and DNA [Nature 213 (1967) 119]; (b). it is needed for the appearance of a primary cell, the volume closed by the lipid membrane. There was no information about the ways on how RNA appeared inside that volume for saving the reaction products around. Our hypothesis suggests that one of the starting points in the origination of primary cells was the interaction of nucleic acid and lipid membrane bubbles in the presence of metal (II) ions (which existed in high concentrations in prebiotic conditions), and this resulted in the enclosing of the pro-RNAs inside the lipid membrane. This hypothesis is formulated by us on the basis of experimental biochemical and biophysical studies of the DNA/RNA-phospholipid vesicles interactions in the presence of metal ions (II) fulfilled in the Institute of Biomedical Chemistry, RAMS, Moscow and Institute of Biophysics, RAS, Pushchino. Our belief is that DNA-membrane contacts (DNA-MCs) played an important role in the prokaryotes-to-eukaryotes transition. The model of the confluence of four prokaryotic cells may explain the prokaryotes-to-eukaryotes transition by the way of eukaryotic nuclear pore formation from prokaryotic Bayer' contacts. The main requirement for the following fusion of prokaryotic cells must be their mutual orientation. After possible association, the division of the formed cell is begun. The great advantage of the model of four prokaryotic cells is the profit in the metabolism and the possibility of the intensive growth of intercellular membrane structures.

The parametric pump mechanism in separation of components in heterogeneous systems. I. Macroscopic distributed systems.

A dynamic method is proposed for the separation of the electrolyte components using a parametric pump with an ion exchange column. It was studied experimentally and described mathematically. The parametric separation of mixtures is based on interactions of two oscillating fields with a heterogeneous system containing two phases, a liquid and a solid one, the components of the mixture being able to redistribute between the phases. The field of mechanical force is responsible for cyclic relative displacement of the phases, and synchronously changing temperature causes redistribution of the components between them. This results in sodium and potassium fluxes opposite in direction which in turn leads to accumulation of sodium and potassium in opposite end cells.

Cooperative dynamics of quasi-1D lipid structures and lateral transport in biological membranes.

A model for the dynamics of quasi-1D lipid structures in biological membranes is proposed. The model takes into account interactions between the lipid heads and hydro-carbon chains, the description of their relaxation dynamics being based on the phenomenological Ginzburg-Landau approach. It is shown that in lateral linear structures of lipids, a soliton-like excitation can propagate with constant velocity. The latter in turn may provide for lateral transport of matter and for membrane conformation changes.