Biomedical subjects

Alexei V Tkachenko

Publications and source records attributed to Alexei V Tkachenko.

9 recordsLinked to original sources

PubMed2006

Statistical mechanics of DNA-mediated colloidal aggregation.

We present a statistical mechanical model of aggregation in colloidal systems with DNA-mediated interactions. We obtain a general result for the two-particle binding energy in terms of the hybridization free energy DeltaG of DNA and two model-dependent properties: the average number of available DNA bridges and the effective DNA concentration c(eff). We calculate these parameters for a particular DNA bridging scheme. The fraction of all the n-mers, including the infinite aggregate, are shown to be universal functions of a single parameter directly related to the two-particle binding energy. We explicitly take into account the partial ergodicity of the problem resulting from the slow DNA binding-unbinding dynamics, and introduce the concept of angular localization of DNA linkers. In this way, we obtain a direct link between DNA thermodynamics and the global aggregation and melting properties in DNA-colloidal systems. The results of the theory are shown to be in quantitative agreement with two recent experiments with particles of micron and nanometer size.

Colloids↗

PubMed2006

Errorproof programmable self-assembly of DNA-nanoparticle clusters.

We study theoretically a generic scheme of programmable self-assembly of nanoparticles into clusters of desired geometry. The problem is motivated by the feasibility of highly selective DNA-mediated interactions between colloidal particles. By analyzing both a simple generic model and a more realistic description of a DNA-colloidal system, we demonstrate that it is possible to suppress the glassy behavior of the system, and to make the self-assembly nearly errorproof. This regime requires a combination of stretchable interparticle linkers (e.g., sufficiently long DNA), and a soft repulsive potential. The jamming phase diagram and the error probability are computed for several types of clusters. The prospects for the experimental implementation of our scheme are also discussed.

Journal Article↗

PubMed2006

Self-assembly of DNA-coded nanoclusters.

We present a theoretical discussion of a self-assembly scheme which makes it possible to use DNA to uniquely encode the composition and structure of microparticle and nanoparticle clusters. These anisotropic DNA-decorated clusters can be further used as building blocks for hierarchical self-assembly of larger structures. We address several important aspects of possible experimental implementation of the proposed scheme: the competition between different types of clusters in a solution, possible jamming in an unwanted configuration, and the degeneracy due to symmetry with respect to particle permutations.

Colloids↗

PubMed2006

Electrostatic effects in DNA stretching.

The response of a semiflexible polyelectrolyte chain to stretching in the regimes of moderate and weak screening is studied theoretically, with a special focus on DNA experiments. By using the nonlinear Poisson-Boltzmann description of electrostatic self-interactions of the chain, we explicitly demonstrate the applicability of the concept of effective charge to certain aspects of the problem. This charge can be extracted from the far-field asymptotic behavior of the electrostatic potential of the fully aligned chain. Surprisingly, in terms of the effective charge, the electrostatically renormalized persistence length can be formally described by the classical Odijk-Skolnick-Fixman formula, whose domain of applicability is normally limited to the linearized Debye-Hückel (DH) approximation. However, the short-scale behavior of the chain in the nonlinear regime deviates from the of DH-based result, even upon charge renormalization. This difference is revealed in the calculated stretching curves for strongly charged DNA. These results are in good agreement with recent experiments. In the limit of weak screening we predict the elastic response to have a distinctive two-stage character, with a peculiar intermediate "unstretchable" regime.

Computer Simulation↗

PubMed2005

Effects of kinks on DNA elasticity.

We study the elastic response of a wormlike polymer chain with reversible kinklike structural defects. This is a generic model for (a) the double-stranded DNA with sharp bends induced by binding of certain proteins, and (b) effects of trans-gauche rotations in the backbone of the single-stranded DNA. The problem is solved both analytically and numerically by generalizing the well-known analogy to the quantum rotator. In the small stretching force regime, we find that the persistence length is renormalized due to the presence of the kinks. In the opposite regime, the response to the strong stretching is determined solely by the bare persistence length with exponential corrections due to the "ideal gas of kinks." This high-force behavior changes significantly in the limit of high bending rigidity of the chain. In that case, the leading corrections to the mechanical response are likely to be due to the formation of multikink structures, such as kink pairs.

Computer Simulation↗

PubMed2005

Disruption of protein-mediated DNA looping by tension in the substrate DNA.

Protein-mediated DNA looping is important in a variety of biological processes, including gene regulation and genetic transformation. Although the biochemistry of loop formation is well established, the mechanics of loop closure in a constrained cellular environment has received less attention. Recent single molecule measurements show that mechanical constraints have a significant impact on DNA looping and motivate the need for a more comprehensive characterization of the effects of tension. By modeling DNA as a wormlike chain, we calculate how continuous stretching of the substrate DNA affects the loop formation probability. We find that when the loop size is >100 bp, a tension of 500 fN can increase the time required for loop closure by two orders of magnitude. This force is small compared to the piconewton forces that are associated with RNA polymerases and other molecular motors, indicating that intracellular mechanical forces might affect transcriptional regulation. In contrast to existing theory, we find that for loops <200 bp, the effect of tension is partly dependent on the relative orientation of the DNA-binding domains in the linker protein. Our results provide perspective on recent DNA looping experiments and suggestions for future micromechanical studies.

Computer Simulation↗

PubMed2004

Unfolding and unzipping of single-stranded DNA by stretching.

We present a theoretical study of single-stranded DNA under stretching. Within the proposed framework, the effects of base pairing on the mechanical response of the molecule can be studied in combination with an arbitrary underlying model of chain elasticity. In a generic case, we show that the stretching curve of single-stranded DNA exhibits two distinct features: the second-order "unfolding" phase transition, and a sharp crossover, reminiscent of the first-order "unzipping" transition in double-stranded DNA. We apply the theory to the particular cases of wormlike chain and freely jointed chain models, and discuss the universal and model-dependent features of the mechanical response of single-stranded DNA. In particular, we show that variation of the width of the unzipping crossover with interaction strength is very sensitive to the energetics of hairpin loops. This opens another way of testing the elastic properties of ssDNA.

Base Pairing↗

PubMed2004

Kinetic pinning and biological antifreezes.

Biological antifreezes protect cold-water organisms from freezing. An example is the antifreeze proteins (AFP's) that attach to the surface of ice crystals and arrest growth. The mechanism for growth arrest has not been heretofore understood in a quantitative way. We present a complete theory based on a kinetic model. We use the "stones on a pillow" picture. Our theory of the suppression of the freezing point as a function of the concentration of the AFP is quantitatively accurate. It gives a correct description of the dependence of the freezing point suppression on the geometry of the protein, and might lead to advances in design of synthetic AFP's.

Antifreeze Proteins↗

PubMed2002

Morphological diversity of DNA-colloidal self-assembly.

We study theoretically a binary system in which an attraction of unlike particles is combined with a type-independent soft-core repulsion. The possible experimental implementation of the system is a mixture of DNA-covered colloids, in which both the repulsion and the attraction may be induced by DNA solution. The system is shown to exhibit surprisingly diverse and unusual morphologies. Among them are the diamond lattice and the membrane phase with in-plane square order, a striking example of spontaneous compactification.

Colloids↗