Force induced DNA melting in the presence of an attractive surface.

The self avoiding walk (SAW) model of the polymer has been extended to study the equilibrium properties of double stranded DNA (dsDNA) where two strands of the dsDNA are modeled by two mutually attracting self-avoiding walks (MASAWs) in the presence of an attractive surface. We study simultaneous adsorption and force induced melting transitions and explore different phases of DNA. It is observed that melting is entropically dominated, which can be substantially reduced under the application of an applied force. We consider three scenarios, where the surface is weakly, moderately and highly attractive. For both weakly and moderately attractive surfaces, the DNA desorbs from the surface in a zipped form and acquires the conformation of a melted state with the rise in temperature. However, for a strongly attractive surface, the force applied at one end of the strand (strand-II) results in unzipping, while the other strand (strand-I) remains adsorbed on the surface. We identify this as adsorption-induced unzipping, where the force applied on a single strand (strand-II) can unzip the dsDNA if the surface interaction energy exceeds a specific threshold. We also note that at a moderate surface attraction, the desorbed-zipped DNA melts with an increase in temperature and the free strand (strand-I) gets re-adsorbed onto the surface.

Effect of solvent gradient inside the entropic trap on polymer migration.

By employing the exact enumeration technique on the lattice model of a polymer, we study the migration of the polymer chain across an entropic trap in a quasiequilibrium condition and explore the effect of solvent gradient present in the entropic trap which acts both parallel and perpendicular to the direction of migration. The Fokker-Planck formalism utilizes the free energy landscape of a polymer chain across the channel in the presence of the entropic trap to calculate the migration time. It is revealed that the migration is fast when the solvent gradient acts along the migration axis (i.e., x axis) inside the channel in comparison to the channel having the entropic trap. We report here for the first time that the entropic trap makes the migration faster at a certain value of solvent gradient. We also study the effect of transverse solvent gradient (along the y axis) inside the trap and investigate the structural changes of the polymer during migration through the channel. We observe the nonmonotonic dependence of migration time on the solvent gradient.

Effect of polydispersity on the dynamics of active Brownian particles.

We numerically study the dynamics and the phases of self-propelled disk-shaped particles of different sizes with soft repulsive potential in two dimensions. Size diversity is introduced by the polydispersity index (PDI) ε, which is the width of the uniform distribution of the particle's radius. The self-propulsion speed of the particles controls the activity v. We observe enhanced dynamics for large size diversity among the particles. We calculate the effective diffusion coefficient D_{eff} in the steady state. The system exhibits four distinct phases, jammed phase with small D_{eff} for small activity and liquid phase with enhanced D_{eff} for large activity. The number fluctuation is larger and smaller than the equilibrium limit in the liquid and jammed phases, respectively. Further, the jammed phase is of two types: solid jammed and liquid jammed for small and large PDI. Whereas the liquid phase is called motility induced phase separation (MIPS) liquid for small PDI and for large PDI, we find enhanced diffusivity and call it the pure liquid phase. The system is studied for three packing densities ϕ, and the response of the system for polydispersity is the same for all ϕ's. Our study can help understand the behavior of cells of various sizes in a tissue, artificial self-driven granular particles, or living organisms of different sizes in a dense environment.

Controlled DNA Delivery Using Poly(lactide) Nanoparticles and Understanding the Binding Interactions.

Cationic polymer-based gene delivery vectors suffer from several limitations such as low DNA-loading capacity, poor transfection, toxicity, environmental degradations, etc. Again, very limited works are available addressing the binding interactions in detail at the atomic level explaining the loading capacity, protection ability against harsh environments, and controlled release behavior of the DNA-encapsulated vehicles. Here, a poly(l-lactide) (PLA) nanoparticle-based controlled DNA release system is proposed. The developed vehicle possesses a high DNA-loading capacity and can release the loaded DNA in a controlled manner. Spectroscopic, physicochemical, and molecular simulation techniques (AM1 and atomistic molecular dynamics) have been employed to understand the binding interactions between PLA and DNA molecules enabling high DNA loading, protection against external harsh environments, and controlled DNA release behavior. Methyl thiazolyl tetrazolium (MTT) assay experiments confirm the biocompatible nature of the vehicle. Cellular uptake efficiency and endo-lysosomal escape capabilities have been investigated against HeLA cells. This study, therefore, demonstrates the development of a promising nonviral DNA delivery vector and includes a detailed investigation of the atomic-level interaction behavior between PLA and DNA molecules.

Scaling of hysteresis loop of interacting polymers under a periodic force.

Using Langevin dynamics simulations, we study a simple model of interacting-polymer under a periodic force. The extension curves strongly depend on the magnitude of the amplitude (F) and the frequency (ν) of the applied force. In low frequency limit, the system retraces the thermodynamic path. At higher frequencies, response time is greater than the external time scale for change of force, which restrict the biomolecule to explore a smaller region of phase space that results in hysteresis of different shapes and sizes. We show the existence of dynamical transition, where area of hysteresis loop approaches to a large value from nearly zero value with decreasing frequency. The area of hysteresis loop is found to scale as F(α)ν(ß) for the fixed length. These exponents are found to be the same as of the mean field values for a time dependent hysteretic response to periodic force in case of the isotropic spin.

Role of loop entropy in the force induced melting of DNA hairpin.

Dynamics of a single stranded DNA, which can form a hairpin have been studied in the constant force ensemble. Using Langevin dynamics simulations, we obtained the force-temperature diagram, which differs from the theoretical prediction based on the lattice model. Probability analysis of the extreme bases of the stem revealed that at high temperature, the hairpin to coil transition is entropy dominated and the loop contributes significantly in its opening. However, at low temperature, the transition is force driven and the hairpin opens from the stem side. It is shown that the elastic energy plays a crucial role at high force. As a result, the force-temperature diagram differs significantly with the theoretical prediction.

Force induced unfolding of biopolymers in a cellular environment: a model study.

Effect of molecular crowding and confinement experienced by protein in the cell during unfolding has been studied by modeling a linear polymer chain on a percolation cluster. It is known that internal structure of the cell changes in time, however, they do not change significantly from their initial structure. In order to model this we introduce the correlation among the different disorder realizations. It was shown that the force-extension behavior for correlated disorder in both constant force ensemble and constant distance ensemble is significantly different than the one obtained in absence of molecular crowding.

Effects of molecular crowding on stretching of polymers in poor solvent.

We consider a linear polymer chain in a disordered environment modeled by percolation clusters on a square lattice. The disordered environment is meant to roughly represent molecular crowding as seen in cells. The model may be viewed as the simplest representation of biopolymers in a cell. We show the existence of intermediate states during stretching arising as a consequence of molecular crowding. In the constant distance ensemble the force-extension curves exhibit oscillations. We observe the emergence of two or more peaks in the probability distribution curves signaling the coexistence of different states and indicating that the transition is discontinuous unlike what is observed in the absence of molecular crowding.

Stretching of a single-stranded DNA: evidence for structural transition.

Recent experiments have shown that the force-extension (F-x) curve for single-stranded DNA (ssDNA) consisting only of adenine [poly(dA)] is significantly different from thymine [poly(dT)]. Here, we show that the base stacking interaction is not sufficient to describe the F-x curves as seen in the experiments. A reduction in the reaction coordinate arising from the formation of helix at low forces and an increase in the distance between consecutive phosphates of unstacked bases in the stretched state at high force in the proposed model qualitatively reproduce the experimentally observed features. The multistep plateau in the F-x curve is a signature of structural change in ssDNA.

Does changing the pulling direction give better insight into biomolecules?

Single-molecule manipulation techniques reveal that the mechanical resistance of a protein depends on the direction of the applied force. Using a lattice model of polymers, we show that changing the pulling direction leads to different phase diagrams. The simple model proposed here indicates that in one case the system undergoes a transition akin to the unzipping of a beta sheet, while in the other case the transition is of a shearing (slippage) nature. Our results are qualitatively similar to experimental results. This demonstrates the importance of varying the pulling direction since this may yield enhanced insights into the molecular interactions responsible for the stability of biomolecules.

Probability distribution analysis of force induced unzipping of DNA.

We present a semimicroscopic model of dsDNA by incorporating the directional nature of hydrogen bond to describe the force induced unzipping transition. Using exact enumeration technique, we obtain the force-temperature and the force-extension curves and compare our results with the other models of dsDNA. The model proposed by us is rich enough to describe the basic mechanism of dsDNA unzipping and predicts the existence of an "eye phase." We show oscillations in the probability distribution function during unzipping. Effects of stacking energies on the melting profile have also been studied.

Effects of the eye phase in DNA unzipping.

The onset of the "eye phase" (a phase consisting of configurations of eye-type conformations or bubbles in the double-stranded DNA) and its role during the DNA unzipping is studied when a force is applied to the interior of the chain. The directionality of the hydrogen bond introduced here shows oscillations in force-extension curve similar to a "sawtooth" kind of oscillations seen in the protein unfolding experiments. The effects of intermediates (hairpins) and stacking energies on the melting profile have also been discussed.

Force-induced conformational transition in a system of interacting stiff polymers: application to unfolding.

We consider a stiff polymer chain in poor solvent and apply a force at one end of the chain. We find that by varying the stiffness parameter, the polymer undergoes a transition from the globule state to the foldedlike state. The conformation of the folded state mimics the beta sheet as seen in the titin molecule. Using the exact enumeration technique, we study the extension-force and force-temperature diagrams of such a system. The force-temperature diagram shows the re-entrance behavior for a flexible chain. However, for a stiff chain this re-entrance behavior is absent and there is an enhancement in theta temperature with the rise of stiffness. We further propose that the internal information about the frozen structure of a polymer can be read from the distribution of end-to-end distance which shows a sawtoothlike behavior.

Force-induced triple point for interacting polymers.

We show the existence of a force induced triple point in an interacting polymer problem that allows two zero-force thermal phase transitions. The phase diagrams for two different models of mutually attracting but self-avoiding polymers are presented. One of these models has an intermediate phase and it shows a triple point. A general phase diagram with multicritical points in an extended parameter space is also discussed.

Adsorption and collapse transitions in a linear polymer chain near an attractive wall.

We deduce the qualitative phase diagram of a long flexible neutral polymer chain immersed in a poor solvent near an attracting surface using phenomenological arguments. The actual positions of the phase boundaries are estimated numerically from series expansion up to 19 sites of a self-attracting self-avoiding walk in three dimensions. In two dimensions, we calculate phase boundaries analytically in some cases for a partially directed model. Both the numerical and analytical results corroborate the proposed qualitative phase diagram.