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Biomedical subjects

M Muthukumar

Publications and source records attributed to M Muthukumar.

At least 19 recordsLinked to original sources
PubMed2006

Effect of deprotection extent on swelling and dissolution regimes of thin polymer films.

The response of unentangled polymer thin films to aqueous hydroxide solutions is measured as a function of increasing weakly acidic methacrylic acid comonomer content produced by an in situ reaction-diffusion process. Quartz crystal microbalance with energy dissipation and Fourier transform infrared spectroscopy measurements are used to identify four regimes: (I) nonswelling, (II) quasiequilibrium swelling, (III) swelling coupled with partial film dissolution, and (IV) film dissolution. These regimes result from chemical heterogeneity in local composition of the polymer film. The acid-catalyzed deprotection of a hydrophobic group to the methacrylic acid tends to increase the hydrophilic domain size within the film. This nanoscale structure swells in aqueous base by ionization of the methacrylic acid groups. The swollen film stability, however, is determined by the hydrophobic matrix that can act as physical cross-links to prevent dissolution of the polyelectrolyte chains. These observations challenge current models of photoresist film dissolution that do not include the effects of swelling and partial film dissolution on image quality.

Journal Article↗
PubMed2006

Electrostatic origin of the genome packing in viruses.

Many ssRNA/ssDNA viruses bind their genome by highly basic semiflexible peptide arms of capsid proteins. Here, we show that nonspecific electrostatic interactions control both the length of the genome and genome conformations. Analysis of available experimental data shows that the genome length is linear in the net charge on the capsid peptide arms, irrespective of the actual amino acid sequence, with a proportionality coefficient of 1.61 +/- 0.03. This ratio is conserved across all ssRNA/ssDNA viruses with highly basic peptide arms, and is different from the one-to-one charge balance expected of specific binding. Genomic nucleotides are predicted to occupy a radially symmetric spherical shell detached from the viral capsid, in agreement with experimental data.

Capsid↗
PubMed2006

Entropy and enthalpy of polyelectrolyte complexation: Langevin dynamics simulations.

We report a systematic study by Langevin dynamics simulation on the energetics of complexation between two oppositely charged polyelectrolytes of same charge density in dilute solutions of a good solvent with counterions and salt ions explicitly included. The enthalpy of polyelectrolyte complexation is quantified by comparisons of the Coulomb energy before and after complexation. The entropy of polyelectrolyte complexation is determined directly from simulations and compared with that from a mean-field lattice model explicitly accounting for counterion adsorption. At weak Coulomb interaction strengths, e.g., in solvents of high dielectric constant or with weakly charged polyelectrolytes, complexation is driven by a negative enthalpy due to electrostatic attraction between two oppositely charged chains, with counterion release entropy playing only a subsidiary role. In the strong interaction regime, complexation is driven by a large counterion release entropy and opposed by a positive enthalpy change. The addition of salt reduces the enthalpy of polyelectrolyte complexation by screening electrostatic interaction at all Coulomb interaction strengths. The counterion release entropy also decreases in the presence of salt, but the reduction only becomes significant at higher Coulomb interaction strengths. More significantly, in the range of Coulomb interaction strengths appropriate for highly charged polymers in aqueous solutions, complexation enthalpy depends weakly on salt concentration and counterion release entropy exhibits a large variation as a function of salt concentration. Our study quantitatively establishes that polyelectrolyte complexation in highly charged Coulomb systems is of entropic origin.

Computer Simulation↗
PubMed2006

Langevin dynamics simulations of genome packing in bacteriophage.

We use Langevin dynamics simulations to study the process by which a coarse-grained DNA chain is packaged within an icosahedral container. We focus our inquiry on three areas of interest in viral packing: the evolving structure of the packaged DNA condensate; the packing velocity; and the internal buildup of energy and resultant forces. Each of these areas has been studied experimentally, and we find that we can qualitatively reproduce experimental results. However, our findings also suggest that the phage genome packing process is fundamentally different than that suggested by the inverse spool model. We suggest that packing in general does not proceed in the deterministic fashion of the inverse-spool model, but rather is stochastic in character. As the chain configuration becomes compressed within the capsid, the structure, energy, and packing velocity all become dependent upon polymer dynamics. That many observed features of the packing process are rooted in condensed-phase polymer dynamics suggests that statistical mechanics, rather than mechanics, should serve as the proper theoretical basis for genome packing. Finally we suggest that, as a result of an internal protein unique to bacteriophage T7, the T7 genome may be significantly more ordered than is true for bacteriophage in general.

Bacteriophages↗
PubMed2006

Simulation of polymer translocation through protein channels.

A modeling algorithm is presented to compute simultaneously polymer conformations and ionic current, as single polymer molecules undergo translocation through protein channels. The method is based on a combination of Langevin dynamics for coarse-grained models of polymers and the Poisson-Nernst-Planck formalism for ionic current. For the illustrative example of ssDNA passing through the alpha-hemolysin pore, vivid details of conformational fluctuations of the polymer inside the vestibule and beta-barrel compartments of the protein pore, and their consequent effects on the translocation time and extent of blocked ionic current are presented. In addition to yielding insights into several experimentally reported puzzles, our simulations offer experimental strategies to sequence polymers more efficiently.

Algorithms↗
PubMed2005

Simulations of stochastic sensing of proteins.

We have performed Langevin dynamics and Poisson-Nernst-Planck calculations to simulate detection of proteins by genetically engineered alpha-hemolysin channels. In the recent stochastic sensing experiments, one end of a flexible polymer chain is permanently anchored inside the protein channel at a specified location, and the other end undergoes complexation with an analyte. Our simulations, using coarse-grained modeling, reproduce all essential qualitative results of the electrophysiology measurements of stochastic sensing. In addition, the underlying macromolecular mechanisms behind stochastic sensing are revealed in vivid details. The entropic fluctuations of the conformations of the tethered polymer chain dictate crucially the unique signatures of the ionic current trace of the channel and provide design rules for successful stochastic sensing. The origin of strong fluctuations in the ionic current of the channel is found to arise from the obstruction of the entrance at the beta-barrel of the channel by the fluctuating segments of the tether. Silencing of the pore is due to the suppression of conformational fluctuations of the chain, and the permanent blockade of ionic current is due to the threading of the tether through the channel. The onset of silencing and permanent blockade of the channel current cannot necessarily be attributed to the capture of analytes. In order for detection events to be timed accurately, the length and anchoring location of the tether must be tuned appropriately.

Bacterial Toxins↗
PubMed2005

Langevin dynamics of semiflexible polyelectrolytes: rod-toroid-globule-coil structures and counterion distribution.

We have investigated the nature of counterion condensation on uniformly charged semiflexible polyelectrolyte chains and the concomitant configurations by monitoring the role of chain stiffness, chain length, counterion valency, and the strength of electrostatic interaction. The counterion condensation is seen to follow the adsorption process and the effective polymer charge increases with chain stiffness. Size and shape, as calculated through the radius of gyration, effective persistence length, and hydrodynamic radius, are studied. Stable coil-like, globular, folded-chain, toroidal, and rodlike configurations are possible at suitable combinations of values of chain stiffness, chain length, electrostatic interaction strength, and the valency of counterion. For high strengths of electrostatic interactions, sufficiently stiff polyelectrolytes form toroids in the presence of multivalent counterions, whereas flexible polyelectrolytes form disordered globules. The kinetic features of the nucleation and growth of toroids are monitored. Several metastable structures are found to frustrate the formation of toroids. The generic pathway involves the nucleation of one primary loop somewhere along the chain contour, followed by a growth process where the rest of the chain is folded continuously on top of the primary loop. The dependence of the average radii of toroids on the chain length is found to be roughly linear, in disagreement with existing scaling arguments.

Adsorption↗
PubMed2005

Effect of chilling, polyphosphate and bicarbonate on quality characteristics of broiler breast meat.

1. An experiment was conducted to assess the effect of tetrasodium pyrophosphate and sodium bicarbonate on colour and sensory attributes of pre- and post-chilled breast meat. 2. Three groups of 6 halves of breasts (pre-chill) immediately after slaughter were treated with 3% tetrasodium pyrophosphate, 3% sodium bicarbonate in 2% NaCl or 2% NaCl alone (control); the remaining 6 halves (post-chill) were stored overnight at 4 degrees C and then treated similarly. Both the pre- and post-chill samples were held at 4 degrees C for 24 h and pH, water holding capacity, cooking loss, CIE colour values and sensory attributes were recorded. 3. Chilling had few effects on the meat characteristics measured in this study. 4. Treatment with phosphate and bicarbonate increased pH in both the pre- and post-chill groups. Treated breasts exhibited lower L* and higher a* value (more red) than controls. 5. A sensory evaluation study revealed improvements in colour and other sensory attributes of cooked broiler breast meat in all treated samples compared to the control. 6. The findings suggest that tetrasodium pyrophosphate and sodium bicarbonate, when injected post mortem, will have beneficial effects on several physico-chemical (pH, colour, WHC %, cooking loss) and sensory attributes of broiler meat. However, phosphate had a smaller effect than bicarbonate.

Animals↗
PubMed2004

Theory of counter-ion condensation on flexible polyelectrolytes: adsorption mechanism.

A new model is presented for counterion distribution around flexible polyelectrolytes by considering (i) free energy of the polyelectrolyte chain, (ii) translational entropy of adsorbed counterions, (iii) adsorption energy, (iv) translational entropy of unadsorbed counterions, (v) fluctuations of dissociated ions, and (vi) correlation among ion-pairs formed by adsorbed counterions on the polymer. The effective charge and size of the polymer are calculated self-consistently. The degree of ionization f of the polymer decreases continuously with 1/epsilonT (epsilon and T are the dielectric constant of the solvent and temperature, respectively), depending sensitively on local dielectric heterogeneity. Further, f decreases with an increase in salt concentration, monomer concentration, or chain flexibility. The polymer size, accompanying the changes in f, depends nonmonotonically on 1/epsilonT. The predictions of the model are consistent with all trends observed previously in simulations and are distinctly different from the Manning argument for rodlike chains.

Adsorption↗
PubMed2004

Polymer translocation through a nanopore. II. Excluded volume effect.

Following our previous study of a Gaussian chain translocation, we have investigated the transport of a self-avoiding chain from one sphere to another sphere through a narrow pore, using the self-consistent field theory formalism. The free energy landscape for polymer translocation is significantly modified by excluded volume interactions among monomers. The free energy barrier for the placement of one of the chain ends at the pore depends on the chain length N nonmonotonically, in contrast to the N-independence for Gaussian chains. This results in a nonmonotonic dependence of the average arrival time [tau0] on N for self-avoiding chains. When the polymer chain is partitioned between the donor and recipient spheres, a local free energy minimum develops, depending on the strength w of the excluded volume interaction and the relative sizes of the donor and recipient spheres. If the sizes of spheres are comparable, the average translocation time tau (the average time taken by the polymer, after the arrival at the pore, to convert from the donor to the recipient) increases with an increase in w for a fixed N value. On the other hand, for the highly asymmetric sizes of the donor and recipient spheres, tau decreases with an increase in w. As in the case of Gaussian chains, tau depends nonmonotonically on the pore length.

Computer Simulation↗
PubMed2003

Triple points in solutions of polydisperse semiflexible polymers.

When a mother solution of semiflexible polymers with differing molecular weights is forced to undergo phase transition, cloud and shadow curves emerge instead of a coexistence curve. For the first time, we calculate the cloud and shadow curves for an isotropic-nematic transition coupled to polydispersity and predict novel triple points. Because of the emergence of new triple points, polydispersity allows the occurrence of anisotropic phases at much lower polymer concentrations than for the monodisperse solutions.

Microtubules↗
PubMed2003

Molecular modelling of nucleation in polymers.

We have investigated the molecular mechanisms of primordial stages of polymer crystallization from solutions using Langevin dynamics simulations and theoretical models. The key feature that distinguishes polymers from small molecules at early stages of nucleation is that, in the case of polymers, a single chain can participate in several nuclei. This results in entropic frustration, leading to spontaneously selected temporary finite structures during nucleation. The experimental observation of finite lamellar thickness (much smaller than extended chain dimension) has been historically attributed to kinetic origins. Our simulations and an exactly solvable model to account for chain entropy show that the finite lamellar thickness is actually the equilibrium result. The growth at the lamellar growth front is found in our simulations to be dominated by chain adsorption and highly cooperative dynamics of all chains. Our results contradict the conventional assumptions and theories of polymer crystallization.

Crystallization↗
PubMed2001

Molecular mechanisms of polymer crystallization from solution.

Our simulations of polymer crystallization from solutions show that (1) entropic barriers control the selection of the initial lamellar thickness, (2) growth at the crystalline interface is chain adsorption followed by crystallographic registry, and (3) lamellar thickening is a highly cooperative process requiring the mobility of all chains in the crystal. These results, especially the latter, challenge the conventional Lauritzen-Hoffman theory and its generalizations.

Journal Article↗
PubMed2001

Translocation of a confined polymer through a hole.

Based on an analogy between polymer translocation across a free energy barrier associated with polymer worming through a hole and classical nucleation and growth process, the escape time tau is predicted asymptotically to be N(N/rho)(1/3nu). N is the polymer length, rho is the monomer density prior to escape, and nu is the radius of gyration exponent. Monte Carlo simulation data collected in the high salt limit (nu approximately 3/5) are in agreement with the asymptotic law and provide vivid details of the escape.

DNA↗
PubMed1996

Theory of electrophoretic mobility of a polyelectrolyte in semidilute solutions of neutral polymers.

An explicit formula is derived for the electrophoretic mobility of a polyelectrolyte molecule in a semidilute solution of neutral polymers in terms of the molecular weight N of a polyelectrolyte, concentration c of neutral polymers, Debye length and solvent quality. The nature of the crossover between different regimes, as c, N, and the salt concentration are varied, is presented. The calculations show that one progressively enters into regimes of no-separation, separation, and no-separation in the electrophoresis of polyelectrolytes as c is increased. If c is very high, one returns to the mechanism of separation in gel electrophoresis.

Electrolytes↗