Kim Ø. Rasmussen

DNA breathing dynamics in the presence of a terahertz field

We consider the influence of a terahertz field on the breathing dynamics of double-stranded DNA. We model the spontaneous formation of spatially localized openings of a damped and driven DNA chain, and find that linear instabilities lead to dynamic dimerization, while true local strand separations require a threshold amplitude mechanism. Based on our results we argue that a specific terahertz radiation exposure may significantly affect the natural dynamics of DNA, and thereby influence intricate molecular processes involved in gene expression and DNA replication.

Bubble Nucleation and Cooperativity in DNA Melting

The onset of intermediate states (denaturation bubbles) and their role during the melting transition of DNA are studied using the Peyrard-Bishop-Dauxois model by Monte Carlo simulations with no adjustable parameters. Comparison is made with previously published experimental results finding excellent agreement. Melting curves, critical DNA segment length for stability of bubbles, and the possibility of a two-state transition are studied.

Sequence-specific thermal fluctuations identify start sites for DNA transcription

We report successful comparisons between model predictions for intrinsic thermal openings and experimental transcription data, showing that large and slow thermally induced openings (bubbles) of double-stranded DNA coincide with the location of start sites for transcription. Investigating viral and bacteriophage DNA gene promoter segments, we find that the largest opening occurs at the transcription start site in all cases studied. Other probable large openings predicted in our model appear to be related to other regulatory sites. The coherent dynamics is determined by a combination of sequence specificity (disorder), nonlinearity, and entropy, controlled by the long-range consequences of local base-pair stacking constraints.

Three-Dimensional Elastic Compatibility and Varieties of Twins in Martensites

We model a cubic-to-tetragonal martensitic transition by a Ginzburg-Landau free energy in the symmetric strain tensor. We show in three dimensions (3D) that solving the St. Venant compatibility relations for strain, treated as independent field equations, generates three anisotropic long-range potentials between the two order parameter components. These potentials encode 3D discrete symmetries, express the energetics of lattice integrity, and determine 3D textures. Simulation predictions include twins with temperature-varying orientation, helical twins, competing metastable states, and compatibility-induced elastic frustration. Our approach also applies to improper ferroelastics.

Mammalian Stem Cells Reprogramming in Response to Terahertz Radiation

We report that extended exposure to broad-spectrum terahertz radiation results in specific changes in cellular functions that are closely related to DNA-directed gene transcription. Our gene chip survey of gene expression shows that whereas 89% of the protein coding genes in mouse stem cells do not respond to the applied terahertz radiation, certain genes are activated, while other are repressed. RT-PCR experiments with selected gene probes corresponding to transcripts in the three groups of genes detail the gene specific effect. The response was not only gene specific but also irradiation conditions dependent. Our findings suggest that the applied terahertz irradiation accelerates cell differentiation toward adipose phenotype by activating the transcription factor peroxisome proliferator-activated receptor gamma (PPARG). Finally, our molecular dynamics computer simulations indicate that the local breathing dynamics of the PPARG promoter DNA coincides with the gene specific response to the THz radiation. We propose that THz radiation is a potential tool for cellular reprogramming.

Models for energy and charge transport and storage in biomolecules.

Two models for energy and charge transport and storage in biomolecules are considered. A model based on the discrete nonlinear Schrödinger equation with long-range dispersive interactions (LRIs) between base pairs of DNA is offered for the description of nonlinear dynamics of the DNA molecule. We show that LRIs are responsible for the existence of an interval of bistability where two stable stationary states, a narrow, pinned state and a broad, mobile state, coexist at each value of the total energy. The possibility of controlled switching between pinned and mobile states is demonstrated. The mechanism could be important for controlling energy storage and transport in DNA molecules. Another model is offered for the description of nonlinear excitations in proteins and other anharmonic biomolecules. We show that in the highly anharmonic systems a bound state of Davydov and Boussinesq solitons can exist.

Exact solutions of the saturable discrete nonlinear Schrödinger equation

Exact solutions to a nonlinear Schrodinger lattice with a saturable nonlinearity are reported. For finite lattices we find two different standing-wave-like solutions, and for an infinite lattice we find a localized soliton-like solution. The existence requirements and stability of these solutions are discussed, and we find that our solutions are linearly stable in most cases. We also show that the effective Peierls-Nabarro barrier potential is nonzero thereby indicating that this discrete model is quite likely nonintegrable.

A nonlinear dynamic model of DNA with a sequence-dependent stacking term

No simple model exists that accurately describes the melting behavior and breathing dynamics of double-stranded DNA as a function of nucleotide sequence. This is especially true for homogenous and periodic DNA sequences, which exhibit large deviations in melting temperature from predictions made by additive thermodynamic contributions. Currently, no method exists for analysis of the DNA breathing dynamics of repeats and of highly G/C- or A/T-rich regions, even though such sequences are widespread in vertebrate genomes. Here, we extend the nonlinear Peyrard–Bishop–Dauxois (PBD) model of DNA to include a sequence-dependent stacking term, resulting in a model that can accurately describe the melting behavior of homogenous and periodic sequences. We collect melting data for several DNA oligos, and apply Monte Carlo simulations to establish force constants for the 10 dinucleotide steps (CG, CA, GC, AT, AG, AA, AC, TA, GG, TC). The experiments and numerical simulations confirm that the GG/CC dinucleotide stacking is remarkably unstable, compared with the stacking in GC/CG and CG/GC dinucleotide steps. The extended PBD model will facilitate thermodynamic and dynamic simulations of important genomic regions such as CpG islands and disease-related repeats.

Specificity and Heterogeneity of Terahertz Radiation Effect on Gene Expression in Mouse Mesenchymal Stem Cells

We report that terahertz (THz) irradiation of mouse mesenchymal stem cells (mMSCs) with a single-frequency (SF) 2.52 THz laser or pulsed broadband (centered at 10 THz) source results in irradiation specific heterogenic changes in gene expression. The THz effect depends on irradiation parameters such as the duration and type of THz source, and on the degree of stem cell differentiation. Our microarray survey and RT-PCR experiments demonstrate that prolonged broadband THz irradiation drives mMSCs toward differentiation, while 2-hour irradiation (regardless of THz sources) affects genes transcriptionally active in pluripotent stem cells. The strictly controlled experimental environment indicates minimal temperature changes and the absence of any discernable response to heat shock and cellular stress genes imply a non-thermal response. Computer simulations of the core promoters of two pluripotency markers reveal association between gene upregulation and propensity for DNA breathing. We propose that THz radiation has potential for non-contact control of cellular gene expression.

Pattern formation in the bistable Gray-Scott model

This paper presents a computer simulation study of a variety of far-from-equilibrium phenomena that can arise in a bistable chemical reaction-diffusion system which also displays Turing and Hopf instabilities. The Turing bifurcation curve and the wave number for the patterns of maximum linear growth rate are obtained from a linear stability analysis. The distribution in parameter space of a wide variety of different spatio-temporal attractors that can be reached through a strong, local perturbation of the linearly stable homogeneous steady state is mapped out. These include global Turing structures, stable localized structures, interacting fronts, mixed Turing-Hopf modes, and spatio-temporal chaos. Special emphasis is given to the newly discovered spot multiplication process in which cell-like structures replicate themselves until they occupy the entire system. We also present results on the formation of lace-like patterns.