Biomedical subjects

E B Zhulina

Publications and source records attributed to E B Zhulina.

10 recordsLinked to original sources

PubMed2006

Hybridization at a surface: the role of spacers in DNA microarrays.

Flexible spacer chains are utilized to enhance the hybridization of terminally anchored oligonucleotide probes of DNA microarrays. A polymer physics approach identifies an underlying mechanism and yields guidelines for the optimal spacer length in terms of the effect on the equilibrium state. For low grafting densities, the dominant effect arises because of the decimation in the number of accessible chain configurations due to the impenetrable surface. Opposing trends are found for long targets and for short targets. At higher grafting densities, different brush regimes introduce an extra hybridization penalty. A novel brush regime is obtained for long neutral spacers and short targets at intermediate ionic strength where the chain stretching is due to the electrostatic interactions between the probes.

Models, Chemical↗

PubMed2006

Wetting phase diagrams of a polyacid brush with a triple point.

The (pre)wetting behavior of an annealed polyelectrolyte (PE) brush by an electrolyte solution that is strongly segregated from an apolar phase is analyzed. In this complex interface, there are interactions on various length scales. There are short-range interactions with the (uncharged) surface, and there are interactions on the length scale of the brush height. Using either the ionic strength or the water-surface interaction strength as the control parameters, it is possible to approach and induce a wetting transition in this system. The first-order wetting transition, promoted by favorable short-range substrate interactions with the surface, is in competition with the wetting transition controlled by the detachment of the fluid interface from the periphery of the PE brush. The electric double layer on top of the PE brush contributes with a repulsive forces to the disjoining pressure that tends to thicken the wetting film, and therefore, the transition in all cases is first order. Various phase portraits of the wetting phase diagram are envisioned. One of these features the crossing of two prewetting lines. At the crossing point three surface states coexist. This triple point is analyzed in some detail with the help of a molecular-level self-consistent field model.

Journal Article↗

PubMed2006

Curved polymer and polyelectrolyte brushes beyond the Daoud-Cotton model.

We revise the classical Daoud-Cotton (DC) model to describe conformations of polymer and polyelectrolyte chains end-grafted to convex spherical and cylindrical surfaces. In the framework of the DC model, local stretching of chains in the brush does not depend on the degree of polymerization of grafted chains, and the polymer density profile follows a single-exponent power law. This model, however, does not correspond to a minimum in free energy of the curved brush. The nonlocal (NL) approximation exploited in the present paper implies the minimization of the overall free energy of the brush and predicts that the polymer density profile does not follow a single-exponent power law. In the limit of large surface curvature the NL approximation provides the same scaling laws for brush thickness and free energy as the local DC model. Numerical prefactors are however different. Extra extension of chains in the brush interior region leads to larger equilibrium brush thickness and lower free energy per chain. A significant difference between outcomes of the two models is found for brushes formed by ionic polymers, particularly for weakly dissociating (p H-sensitive) polyelectrolytes at low solution salinity.

Journal Article↗

PubMed2005

Brush effects on DNA chips: thermodynamics, kinetics, and design guidelines.

In biology experiments, oligonucleotide microarrays are contacted with a solution of long nucleic acid targets. The hybridized probes thus carry long tails. When the surface density of the oligonucleotide probes is high enough, the progress of hybridization gives rise to a polyelectrolyte brush due to mutual crowding of the nucleic acid tails. The free-energy penalty associated with the brush modifies both the hybridization isotherms and the rate equations: the attainable hybridization is lowered significantly as is the hybridization rate. When the equilibrium hybridization fraction, x(eq), is low, the hybridization follows a Langmuir type isotherm, x(eq)/(1 - x(eq)) = c(t)K where c(t) is the target concentration and K is the equilibrium constant. K is smaller than its bulk value by a factor (n/N)(2/5) due to wall effects where n and N denote the number of bases in the probe and the target. At higher x(eq), when the brush is formed, the leading correction is x(eq)/(1 - x(eq)) = c(t)K exp - const'x(eq)(2/3) - x(B)(2/3) where x(B) corresponds to the onset of the brush regime. The denaturation rate constant in the two regimes is identical. However, the hybridization rate constant in the brush regime is lower, the leading correction being exp -const' x(2/3) - x(B)(2/3).

Computer Simulation↗

PubMed2005

Reentrant morphological transitions in copolymer micelles with pH-sensitive corona.

In contrast to self-assembled aggregates of conventional ionic (including polymeric) surfactants the equilibrium micelles of diblock copolymer with a pH-sensitive polyelectrolyte block can exhibit two inverse sequences of morphological transitions triggered by an increase in solution salinity. The direct sequence of the sphere-cylinder-lamella transitions is similar to that for the copolymer with a strongly dissociating ionic block and occurs at a high salt concentration in solution. The abnormal reversed sequence of the lamella-cylinder-sphere transitions is predicted to occur at relatively low ionic strength in solution. The origin of the reentrant transitions is coupling between aggregation and ionization in copolymer micelles.

Letter↗

PubMed2004

Sensitivity, specificity, and the hybridization isotherms of DNA chips.

Competitive hybridization, at the surface and in the bulk, lowers the sensitivity of DNA chips. Competitive surface hybridization occurs when different targets can hybridize with the same probe. Competitive bulk hybridization takes place when the targets can hybridize with free complementary chains in the solution. The effects of competitive hybridization on the thermodynamically attainable performance of DNA chips are quantified in terms of the hybridization isotherms of the spots. These relate the equilibrium degree of the hybridization to the bulk composition. The hybridization isotherm emerges as a Langmuir isotherm modified for electrostatic interactions within the probe layer. The sensitivity of the assay in equilibrium is directly related to the slope of the isotherm. A simpler description is possible, in terms of c(50) values specifying the bulk composition corresponding to 50% hybridization at the surface. The effects of competitive hybridization are important for the quantitative analysis of DNA chip results, especially when used to study point mutations.

Base Sequence↗

PubMed2003

Annealing polyelectrolytes at charged interfaces.

The conformation of a weakly dissociating (annealing) polyelectrolyte chain end-tethered to a similarly or oppositely charged planar surface is analyzed in the framework of scaling arguments. For a similarly charged interface an analytical model is also utilized. We demonstrate that at low salt concentration in bulk solution there is a strong coupling between the polyelectrolyte conformation and its degree of ionization. In the case of an oppositely charged (adsorbing) surface, adsorption promotes ionization of the annealing polyelectrolyte. As a result, the adsorbed layer thickness decreases as a function of surface charge density more rapidly for an annealing polyelectrolyte than for a quenched one. In the case of a similarly charged (repulsive) surface the chain ionization is suppressed, and the annealing polyelectrolyte chain is less extended than the quenched one. Moreover, an increase in surface charge density leads to non-monotonous extension of the tethered polyelectrolyte.

Journal Article↗

PubMedDate not supplied

[Helix-globule transitions of polypeptides selectively reacting with the interface].

An analytical theory of helix-coil transitions for polypeptides in a solution near a flat and homogeneous interface is given. The following cases were considered: a) only the helical parts are absorbtively active; b) only the coiled sections of the chain are active in adsorption. It has been shown that the binding of the polymer chain to the surface is a result of a phase transition of a second order, moreover in case a) the presence of a secondary structure abruptly increases the ability of the macromolecules to bind to the interface. This largely increases the stability of the helical structure of the chain and leads to a practically complete spiralization of the macromolecule. The profile of the conformational transitions was strictly asymmetrical which is typical for the phase transitions. In case b) the process of binding resembles the adsorbtion of the Gaussian coils. In this case the rate of spiralization of the chain decreases in the course of binding and the degradation of the secondary structure is significant even if the helical state in volume is stable. The profile of the transition remains qualitatively similar to the helix-coil transition in volume but is displaced to the region of larger equilibrium constants.

Models, Chemical↗

PubMedDate not supplied

[The effect of external restrictions on the stability of the globular state].

The delta Td changes of heat denaturation temperature for globule proteins were estimated, for a globule inserted into pores of a inert carrier, that limits the conformational set of the denatured chain. Based on calculations for a grated selfintercepted chain in a slit-like pore, with no interactions with the pore walls, functions of delta Td depending on the rigidity of the unfolded chain, its length and pore sizes were determined. For alpha-chymotrypsin in polyacrylamide gels the estimated delta Td was of several degrees. The possible influence of the pore form and intramolecular interactions for a denatured chain on the value of the stabilizing effect is discussed.

Drug Stability↗

PubMedDate not supplied

[Conformational transitions in adsorbed macromolecules with secondary structure].

An analytical theory is presented taking into account the effects of the flat adsorbing surface on the equilibrium properties of the long single-stranded macromolecule possessing a secondary structure. Change of the secondary structure is described in terms of Zimm--Bragg theory; adsorbtion properties are calculated for the lattice model without taking into account the 3-dimensional interactions. It is shown that the presence of the adsorbing surface sharpens helix-coil transition, displacing it towards the lower constants of equilibrium (s). A relation of the critical energy of adsorbtion (--epsilonkappa) on s is obtained at different values of the cooperativity factor sigma. This relationship represents a phase diagram of the system. Various sections of this phase diagram corresponding to different dependence of s and --epsilon on the external factors are considered. It is shown that the process of adsorbtion may occur in different manners: either cooperatively or by the phase transition of type II with jumps in one or in three points.

Kinetics↗