Processes of DNA condensation induced by multivalent cations: Approximate annealing experiments and molecular dynamics simulations

The condensation of DNA induced by spermine is studied by atomic force microscopy （AFM） and molecular dynamics （MD） simulation in this paper. In our experiments, an equivalent amount of multivalent cations is added to the DNA solutions in different numbers of steps, and we find that the process of DNA condensation strongly depends on the speed of adding cations. That is, the slower the spermine cations are added, the slower the DNA aggregates. The MD and steered molecular dynamics （SMD） simulation results agree well with the experimental results, and the simulation data also show that the more steps of adding multivalent cations there are, the more compact the condensed DNA structure will be. This investigation can help us to control DNA condensation and understand the complicated structures of DNA--cation complexes.

A multi-field approach to DNA condensation

DNA condensation is an important process in many fields including life sciences, polymer physics, and applied technology. In the nucleus, DNA is condensed into chromosomes. In polymer physics, DNA is treated as a semi-flexible molecule and a polyelectrolyte. Many agents, including multi-valent cations, surfactants, and neutral poor solvents, can cause DNA condensation, also referred to as coil–globule transition. Moreover, DNA condensation has been used for extraction and gene delivery in applied technology. Many physical theories have been presented to elucidate the mechanism underlying DNA condensation, including the counterion correlation theory, the electrostatic zipper theory, and the hydration force theory. Recently several single-molecule studies have focused on DNA condensation, shedding new light on old concepts. In this document, the multi-field concepts and theories related to DNA condensation are introduced and clarified as well as the advances and considerations of single-molecule DNA condensation experiments are introduced.

Effect of Torsion on Cisplatin-Induced DNA Condensation

We investigate the effect of torsion on DNA condensation with the covalently closed circular DNA as the torsionconstrained system, using an atomic force microscope. It is found that there are two stages in the DNA condensation process under torsional constraint. At the early stage, the low torsion will accelerate DNA condensation by promoting the formation of micro-loops or intersection structures; while at the later stage, the increasing torsion will slow it down by preventing the crosslinking of cisplatin and DNA since the DNA molecule becomes more rigid. Our results show the important role of torsion in DNA condensation and sheds new light on the mechanism for DNA condensation.

DNA condensation and size effects of DNA condensation agent

Based on the model of the strong correlation of counterions condensed on DNA molecule, by tailoring interaction potential, interduplex spacing and correlation spacing between condensed counterions on DNA molecule and interduplex spacing fluctuation strength, toroidal configuration, rod-like configuration and two-hole configurations are possible. The size effects of counterion structure on the toroidal structure can be detected by this model. The autocorrelation function of the tangent vectors is found as an effective way to detect the structure of toroidal conformations and the generic pathway of the process of DNA condensation. The generic pathway of all of the configurations involves an initial nucleation loop, and the next part of the DNA chain is folded on the top of the initial nucleation loop with different manners, in agreement with the recent experimental results.

Delivery of pOXR1 through an injectable liposomal nanoparticle enhances spinal cord injury regeneration by alleviating oxidative stress

Oxidation resistance 1(OXR1)is regarded as a critical regulator of cellular homeostasis in response to oxidative stress.However,the role of OXR1 in the neuronal response to spinal cord injury(SCI)remains undefined.On the other hand,gene therapy for SCI has shown limited success to date due in part to the poor utility of conventional gene vectors.In this study,we evaluated the function of OXR1 in SCI and developed an available carrier for delivering the OXR1 plasmid(pOXR1).We found that OXR1 expression is remarkably increased after SCI and that this regulation is protective after SCI.Meanwhile,we assembled cationic nanoparticles with vitamin E succinate-graftedε-polylysine(VES-g-PLL)(Nps).The pOXR1 was precompressed with Nps and then encapsulated into cationic liposomes.The particle size of pOXR1 was compressed to 58 nm,which suggests that pOXR1 can be encapsulated inside liposomes with high encapsulation efficiency and stability to enhance the transfection efficiency.The agarose gel results indicated that Nps-pOXR1-Lip eliminated the degradation of DNA by DNase I and maintained its activity,and the cytotoxicity results indicated that pOXR1 was successfully transported into cells and exhibited lower cytotoxicity.Finally,Nps-pOXR1-Lip promoted functional recovery by alleviating neuronal apoptosis,attenuating oxidative stress and inhibiting inflammation.Therefore,our study provides considerable evidence that OXR1 is a beneficial factor in resistance to SCI and that Nps-Lip-pOXR1 exerts therapeutic effects in acute traumatic SCI.