Yu. M. Evdokimov

Effect of Gold Nanoparticles on Mouse Spermatogenesis

The response of the mouse male germ cells exposed to gold nanoparticles (∼2.5 nm) was studied. Our investigation demonstrates that treatment with Au nanoparticles for four days does not impair the architecture of the spermatogenic epithelium. Cytogenetic evaluation using micronucleus assay showed that gold nanoparticles can affect the chromosomes of early primary spermatocytes. However, gold nanoparticles did not induce chromosome abnormalities in spermatogonial stem cells. Further, the cauda epididymal sperm was isolated on the 14th day after treatment and was incubated in SDS solution (Na dodecyl sulphate) and then in a solution containing DTT (dithiothreitol) to induce nuclear chromatin decondensation. Observations showed that after four days of treatment of spermiogenic (postmeiotic) cells with gold nanoparticles the decondensation process had no differences from the control. On the contrary, in the experiment with the same cells and period of fixation but with a single exposure to gold nanoparticles, the number of mature gametes with totally decondensed nuclei reached 100% as opposed to 44% in the controls.

Structural effects induced by gold nanoparticles in particles of cholesteric liquid-crystalline dispersion of double-stranded nucleic acids

Gold (Au) nanoparticles of diameter ~2 nm (but not 5 or 15 nm) were capable of incorporating effectively into quasi-nematic layers of particles of cholesteric liquid-crystalline dispersions (CLCD) formed by double-stranded nucleic acids of various families [B-form DNA, A-form poly(I) × poly(C)]. A study of the properties of CLCD particles treated with Au nanoparticles by various physicochemical methods demonstrated that incorporation of Au nanoparticles into quasi-nematic layers of these particles resulted in two effects. First, it caused rearrangement of the spatial cholesteric structure of LC dispersion particles that was accompanied by a decrease in the amplitude of the anomalous band in the circular dichroism spectrum of the corresponding initial CLCD. Second, it induced Au cluster formation within the LC particles that was accompanied by the appearance of a surface plasmon resonance band in the visible spectral region. It was possible that these structural effects were responsible for the genotoxicity of the Au nanoparticles.

Effect of electroelastic anisotropy of DNA-like molecules on their tertiary structure

Under certain conditions, mechanical forces can cause an anisotropic molecule like DNA to assume a toroidal spatial structure. A simple model describing such a behavior is suggested. The model incorporates anisotropic elastic energy and external electrical forces. The steady-state structures formed by a macromolecule have been studied numerically using this model. There exist ranges of model parameters, namely, the anisotropy of the elastic tensor, magnitude and orientation of forces, and modulation periods, where molecules have toroidal, spherical, or extended structures. Estimates of parameters characteristic of these structures are consistent with experimental data. In particular, the toroidal structure dimension corresponds to experimental dimensions of toroidal globules produced as a result of so-called PSI condensation of DNA molecules.

Complex approach to investigation of the mechanisms of action of antimicrobial and antiviral drugs

Enzyme and biosensor test systems have been used in vitro to study the possible mechanisms of action of antimicrobial and antiviral drugs. It is established that compounds belonging to these groups of drugs may cause various modes of damage in the DNA secondary structure, possess complex-forming properties, inhibit enzymes of the antioxidant protection system of the oganism, induce energy deficiency, and lead to the storage of toxic metabolites (aldehydes).

Asymmetry of the propagation of conformational excitations in a double-strand DNA molecule

A very simple model describing the conformational degrees of freedom of a double-strand DNA molecule is proposed. It is shown that the characteristic modes of the model consist of an acoustic (longitudinal with respect to the axis of the double helix) and two transverse optical modes. The latter modes are directly related with the deformations of the ideal structure of the double helix, which necessarily leads to softening of one of the optical modes on a finite wave vector. It is found that the conformational excitations propagating in DNA are asymmetric.

Dynamics of penetration of “Rigid” nanostructures of double-stranded DNA complexed with gadolinium into CHO cells

Currently, neutron capture therapy is a promising cancer treatment. This method is based on the reaction of thermal neutron capture by some nonradioactive elements (e.g., Gd157), which results in the sub-sequent emission of electrons and gamma rays. An effective instrument for delivering gadolinium into tumor tissue are “rigid” nanostructures (NSs) based on double-stranded DNA complexes with gadolinium (NS-Gd). The local concentration of Gd in these nanostructures may reach 40%. To optimize the process of neutron capture therapy, it is very important to investigate possible mechanisms of the penetration of NS-Gd particles into tumor cells. In this work, the dynamics of interaction between NS-Gd and cultivated Chinese hamster ovary cells (CHO) was studied by confocal and electron microscopy. NS-Gd were shown to be able to enter CHO cells. This process started after about 1 h of incubation. After 6 h, NS-Gd particles were detected in almost all cells. A further increase in the incubation time did not lead to significant changes in cell morphology, although the amount of NS-Gd inside cells continued to increase. The plasma membranes of the cells remained intact. Once entering the cells, NS-Gd particles remained there for a long time. The data show that NS-Gd has relatively low toxicity and suggest that the presence of NS-Gd in tumor cells does not prevent their division. The data are important for improving the efficiency of the method of neutron-capture therapy.

Helical ordering of hydrogen bonds between pairs of DNA bases

The interaction between hydrogen bonds and conformational elastic degrees of freedom has been investigated using the simplest model of a double-strand DNA molecule. The hydrogen bonds are described in terms of two-level quantum systems. After excluding conformational degrees of freedom, one has effective interaction among two-level systems. In the ground state of an ideal double helix, hydrogen bonds in a DNA molecule also have a helical order induced by conformational degrees of freedom. The pitch of the hydrogen-bond helix (and even its sign under certain conditions) is different from that of the basic helix pitch and, generally speaking, is incommensurate with the latter. This effect can, possibly, lead to an inversion of the sign of the circular dichroism in spectral bands, which was detected in some experiments.