Investigaton Of Dynamical And Elastic Properties Of DNA

The mechanical properties of DNA play an important role in its participation in the replication, transcription, recombination and other biological behaviors. But the vast majority of research has focused on its biochemical properties based on base sequence. And there are less studies on DNA’s biomechanical properties, leading to insufficient understanding of some of its mechanical properties. In recent years, the progress of the single molecule measuring techniques, lend people the opportunity to get further knowledge of the mechanical behavior of DNA in very small scales. Using theoretical models to further interpret these accurate measurement results in single-molecule scales, will greatly enhance the understanding of the mechanical properties of DNA and provide guidance to the related biomedical applications. Accruate theoretical models are required to decipher these high-resolution experimental results. In the thesis, I pay attention to several scenarios relevant to physiological conditions, including mechanical behavior in dilute solutions, salt solutions and under tension. I use a variety of theoretical models, together with the supplementary experiments to decipher some of the precision measurement results of single molecule in recent years. These work solve several problems existed in dynamical and elastic properties of double-stranded DNA(ds DNA) and single-stranded DNA(ss DNA). Main work include:.(1) There are reports that the abnormal sub-Zimm dynamics arise for ds DNA in dilute solutions. Using the bead-spring model and mean-field Gaussian model to analyze experimental data to explain the abnormal Zimm-type dynamics. Calculations obtained from bead-spring model show that the ds DNA dynamics fall into a model between Rouse- and Zimm- type. Mean-field Gaussian chain model can reproduce ds DNA end-monomer dynamics of all the relaxation modes in a parameter-free way. Calculations obtained from mean-field Gaussian model further suggest the sub-Zimm scaling of ds DNA in the intermediate regime rise naturally. The stochastic dynamics of ds DNA in solution can promote searching of proteins along the randomly coiled chains, which is 1D/3D facilitate diffusion. Calculations reveal that proteins mainly take 1D diffusion in when the sliding length is smaller than 20 nm, whereas display 3D diffusion in a scale beyond the scale.(2) Elastic properties obtained from large-scale measurements are limited by the accuracy. To counter this problem, I use mean-field Gaussian chain model to accurately predict the experimental measurements of ss DNA monomer dynamics and calculate the accurate persistence length of.ss DNA. Mean-field Gaussian chain model that covers all the relaxation modes would given a much more accurate persistence length than other theoretical deciphering of the classical large-scale measurements. Using Monte Carlo algorithm to implement the optimization, obtaining a persistence length 2.223 nm and length per base 0.676 nm. Obtained Flory’s characteristic ratio of ss DNA is much greater than the classical synthetic polymers, such as polystyrene, polyethylene, indicating a larger swelling degree. Using particle tracking method and digital image processing method to investigate the sequence dependence of ss DNA’s microrheological properties. The experimental results showed that the storage modulus of ss DNA varies with the sequence, while the loss modulus only varies with the sequence in the high frequency regime.The problem of vague scales exist in the studies of charges’ influence on ss DNA, leading to a poor knowledge of the non-electrostatical properties charaterized by the bare persistence length. To deal with this problem, I use scale-separation ideal chain model to investigate the affection of electrostatic interactions for ss DNA’s elasticity and precisely calculate non-electrostatical elasticity. Electrostatic interactions along the ss DNA backbone are strictly divided into proximal and distal interactions. The proximal part contributes to ss DNA’s bending rigidity, and the distal part plays a role in the swelling effects. A bare persistence length of 0.44-0.48 nm is obtained from calculations of Monte Carlo algorithm, much larger than the reported data, indicating a significant contribution of ss DNA’s non-electrostatical electricity to its biomechanical behaviour. Calculations demonstrate bare persistence length of ss DNA contribute significantly to the frequently seen biomechanical parameters, including bending energy, the longest relaxation time, intrinsic viscosity. The contribution percentage may be larger than 50% at high salt concentrations.(4) Models describing force-extension relation of ds DNA and ss DNA do no match with each other. To solve this problem, I use unified ideal chain model to investigate force-induced deformations of ds DNA and ss DNA,and evaluate the crossover force that the polymers transform from a worm-like chain to a freely jointed chain. and can cover the whole force regime corresponding worm-like chain and freely-jointed chain. Using unified ideal chain model to analyze the reported force-extension data of ds DNA and ss DNA, obtaining a crossover force of 5631.85 p N and 84.3 p N respectively. This indicates that when the physiological tension(< 100 p N) is applied, ss DNA transforms from a worm-like chain to freely jointed chain under strong tension, and ds DNA does not undergo such a crossover. Determining the signaling molecules that create intracellular tension with immunofluorescence, and confirm the role of myosin light chain in producing tension. Performing a preliminary study on the influence of tension on ds DNA-protein binding and ss DNA desorption.