Vibrational Modes Of DNA Research Articles

Abstract 817: Assessment and manipulation of DNA methylation in cancer cells using terahertz radiation

Abstract Carcinogenesis is closely associated with abnormal regulation of gene expression, among which DNA methylation in one of the key epigenetic modifications. Therefore, several studies have been directed towards the evaluation of DNA methylation. Here, we aimed to experimentally observe the specific signal of methylated DNA in various blood cancer cell lines using terahertz (THz) radiation, which is presented as a resonance in the spectrum. THz radiations are electromagnetic waves having frequencies of 0.1−10 THz, which falls between those of infrared radiation and microwaves. Molecular low-energy motions in THz region, such as collective vibrations, torsion of molecular structures, and hydrogen bonds, is correlated with biological characteristics, i.e., vibrational modes of DNA, structural modes in proteins, cell membrane vibrations, or enzyme activity. These features are usually presented as a characteristic resonance of the modes in the THz spectrum. In our study, the degree of global DNA methylation was obtained by the quantification of the resonance around 1.7 THz, and the results were in good agreement with those obtained by enzyme-linked immunosorbent assay (ELISA). Further, DNA demethylation was performed using high-power THz radiation around the resonance frequency of 1.7 THz, which lead to a 10% to 72% decrease in the degree of DNA methylation as shown in Table 1. Thus, our data shows the feasibility of using THz radiation for the assessment and manipulation of DNA methylation. This is the first study wherein the sensing and manipulation of DNA methylation could be achieved using a non-contact and non-invasive optical technique. Use of THz radiation for the assessment of DNA methylation might be helpful for its rapid processing, while THz manipulation of DNA methylation can avoid the toxicity of chemical demethylating agents. We propose that THz radiation may be useful for the diagnosis of cancer and we expect that THz demethylation might find potential application in cancer therapy. Change of methylation status of blood cancer DNA using high-power THz radiation.SamplesNo ExposureHigh-power THz exxpsoureChange (%) THzChange (%) ELISATHzELISARatio1THzELISARatio2119.621.8510.6111.661.0611.0040.5742.70211.341.388.2210.201.198.5710.0513.77315.151.4310.596.240.738.5558.8148.95417.731.4712.063.510.447.9880.2070.07511.271.437.8810.001.367.3511.274.90STDEV1.58STDEV1.24THz, the amplitude of terahertz resonance; ELISA, optical density of Enzyme linked immunosorbent assay; STDEV, standard deviation1 THz/ELISA of no exposure2 THz/ELISA of high-power THz exposure Citation Format: Hee-Jin Yang, Hwayeong Cheon, Jin Ho Paik, Joo-Hiuk Son. Assessment and manipulation of DNA methylation in cancer cells using terahertz radiation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 817.

ENVIRONMENTAL EFFECTS INFLUENCING THE VIBRATIONAL MODES OF DNA: NANOSTRUCTURES COUPLED TO BIOMOLECULES

The interactions of charges in DNA with the vibrational modes in DNA depend on the spectra of these vibrational modes. Using (a) the Su-Schrieffer-Heeger (SSH) Hamiltonian approach, (b) integrated structures of DNA and manmade nanostructures, and (c) gel electrophoresis techniques,1 the interaction between charges in DNA and the vibrational modes of DNA are investigated. As is well-known, DNA has a rich spectrum of modes in the THz spectral regime. The use of manmade nanostructures integrated with DNA facilitates the engineering of nanoscale systems useful in studying the role of environmental effects on the vibrational modes of DNA as well as the interaction of these modes with charge carriers in DNA. Among the DNA-based structures considered in this account are: B-DNA and Z-DNA strands related by a conformational change; and DNA molecules bound on one terminal to indirect bandgap semiconductor quantum dots. Gel electrophoresis is used as a tool for the analysis of carrier interactions in novel integrated DNA-manmade-nanostructure complexes, and models based on the SSH Hamiltonian2 are employed as a means of analyzing the interactions between the vibrational modes of DNA and charge carriers in DNA.3-4

Atomistic model of DNA: Phonons and base-pair opening

A fully atomistic model of B-DNA using the CHARMM (chemistry at Harvard molecular mechanics) force field is presented. Molecular dynamics simulations were used to prepare an equilibrium structure. The Hessian of interatomic forces obtained from CHARMM for the equilibrium structure was used as input to a large scale phonon calculation. The calculated dispersion relations at low frequency are compared with recently published experimental data, which shows the model to have good accuracy for the low frequency, vibrational modes of DNA. These are discussed in the context of base-pair opening. In addition to the widely reported modes at, or below, approximately 12.5 meV, a continuous band of modes with strong base-pair opening character is found up to 40 meV, which coincides with the typical denaturation temperature of DNA.

Self-consistent phonon theory of mean-field hydrogen-bond melting of poly(dG)-poly(dC).

A modified self-consistent phonon theory based on the Green's-function method is developed and is applied to a melting of the hydrogen bonds in DNA polymer poly(dG)-poly(dC), where dG refers to repeating guanine bases on one strand and dC the repeating cytosine bases on the other strand. The model predicts melting at 380 K. The calculation has no parameters adjusted to fit the melting and the hydrogen-bond potentials are adjusted to fit data of vibrational modes of DNA at room temperature.