Biophysical Interaction Between Nanoparticles and Biomolecules

In the last two decades nanotechnology market has undergone remarkable growth. Breakthroughs in nanomaterial synthesis increased diverse nanomaterials production and subsequently their application. Owing to its large surface to volume ratio and remarkable physical properties not seen in the bulk materials, nanoparticles are finding emerging use in industry and medicine. Hence, it is expectable that at some point these nanomaterials will end up released into the environment and interact with bio systems. The purpose of this dissertation is to elicit implications of nanomaterial transformation once it gets inside biological milieu

Diameter-Selective Dispersion of Carbon Nanotubes via Polymers: A Competition between Adsorption and Bundling

The mechanism of the selective dispersion of single-walled carbon nanotubes (CNTs) by polyfluorene polymers is studied in this paper. Using extensive molecular dynamics simulations, it is demonstrated that diameter selectivity is the result of a competition between bundling of CNTs and adsorption of polymers on CNT surfaces. The preference for certain diameters corresponds to local minima of the binding energy difference between these two processes. Such minima in the diameter dependence occur due to abrupt changes in the CNT's coverage with polymers and their calculated positions are in quantitative agreement with preferred diameters, reported experimentally. The presented approach defines a theoretical framework for the further understanding and improvement of dispersion/extraction processes.Comment: 22 pages, 5 figures, ACS Nano (2015

Sequence Dependent Interactions and Recognition between DNA and Single-Walled Carbon Nanotubes

Since DNA-SWCNT hybrids have a number of potential biomedical applications such as molecular sensing, drug delivery and cell imaging, it is essential to characterize them and to understand their structure and properties. Certain single stranded DNA (ssDNA) sequences are known to recognize their partner single wall carbon nanotube (SWCNT). We report here the activation energies for removal of several ssDNA sequences from a few SWCNT species by a surfactant molecule. We found that DNA sequences systematically have higher activation energy of dissociation from their carbon-nanotube recognition partner than on non-partner species. Since the difference in binding affinity and difference in partitioning can depend on DNA structure on the single walled carbon nanotube (SWCNT), we studied the partitioning of the various DNA sequences in an aqueous two phase system. We found that for two sequences of same length, (CCA)10 on (6,5) SWCNT requires much higher amount of modulant to be moved from the relatively hydrophilic phase to the more hydrophilic phase as compared to (GT)15 on (6,5), suggesting that the solvation energy depends greatly on the DNA sequence. We also found that various sequences with the same length but different repeating units of two bases exhibit different hydration energies on the same SWCNT (6,5). Unlike the majority of DNA structures in bulk that are stabilized by canonical Watson-Crick pairing between Ade-Thy and Gua-Cyt, those adsorbed on surfaces are often stabilized by non-canonical base pairing, quartet formation, and base-surface stacking. All-atom molecular simulations of DNA bases in two cases - in bulk water and strongly adsorbed on a graphite surface – are conducted to study the relative strengths of stacking and hydrogen bond interactions for each of the ten possible combinations of base pairs. We find that stacking interactions exert the dominant influence on the stability of DNA base pairs in bulk water in the order, Gua-Gua \u3e Ade-Gua \u3e Ade-Ade \u3e Gua-Thy \u3e Gua-Cyt \u3e Ade-Thy \u3e Ade-Cyt \u3e Thy-Thy \u3e Cyt-Thy \u3e Cyt-Cyt. On the other hand, mutual interactions of surface adsorbed base pairs are stabilized mostly by hydrogen bonding interactions in the order, Gua-Cyt \u3e Ade-Gua \u3e Ade-Thy \u3e Ade-Ade \u3e Cyt-Thy \u3e Gua-Gua \u3e Cyt-Cyt \u3e Ade-Cyt \u3e Thy-Thy \u3e Gua-Thy. Interestingly, several non-Watson-Crick base pairings, that are commonly ignored, have similar stabilization free energies due to inter-base hydrogen bonding as Watson-Crick pairs. This clearly highlights the importance of non-Watson-Crick base pairing in the development of secondary structures of oligonucleotides near surfaces. Hybrids of single stranded DNA and single walled carbon nanotubes have proven very successful in separating various chiralities and, very recently, enantiomers of carbon nanotubes using aqueous two-phase separation. This technique sorts objects based on small differences in hydration energy, which is related to corresponding (small) differences in structure. Separation by handedness requires that a given ssDNA sequence adopt different structures on the two SWCNT enantiomers. Here we study the physical basis of such selectivity using a coarse grained model to compute the energetics of ssDNA wrapped around an SWCNT. Our model suggests that difference by handedness of the SWCNT requires spontaneous twist of the ssDNA backbone. We also show that differences depend sensitively on the choice of DNA sequence

Conformations and Dynamics of Semi-Flexible Polymers

In this dissertation, we investigate the conformations, transverse fluctuations and dynamics of two-dimensional (2D) semi-flexible polymers both in the bulk and under channel confinement. We present unified scaling relations in regard to various quantities of interest for a broad range of combinations of chain length and chain stiffness using Langevin dynamics simulation. We also present a three-dimensional (3D) heterogeneous semi-flexible chain model for a double stranded DNA (dsDNA). Our model not only confirms the established findings for homogeneous dsDNA, but also predicts new physical phenomenon for heterogeneous dsDNA. The problems studied in this dissertation are relevant to analysis of the conformations and dynamics of biopolymers (such as DNA) in living organisms, and also offer insights for developing devices which operate on the single-molecule level. In particular, we present a unified description for the dynamics of building-blocks (monomers) of a semi-flexible chain. We consider the full range of flexibility from the case where the chain is fully flexible (no stiffness at all) to the case where the chain behaves like a rod (infinite stiffness). Our theory predicts qualitatively different sub-diffusive regimes for the monomer dynamics originating from the chain stiffness by studying the mean square displacement (MSD) of the monomers before the chain dynamics become purely diffusive. For the conformations in the bulk, we present results confirmed and agreed by two completely different models of semi-flexible polymers, with one of which is the bead-spring model (studied by Langevin dynamics) in the continuum space, the other (studied by Monte Carlo) is a self-avoiding walk chain on the square lattice, where only discrete bond angles are possible. We point out the universal features of chain conformations and fluctuations which are independent of the models. For the conformations under channel confinement, we discover qualitatively different conformations and dynamics of the chain as a function of the channel width and chain stiffness, and show how globule like shapes ( de Gennes blobs ) for more flexible chains continuously go over to shapes in the form of deflections from the wall ( Odijk limit ) for more stiff chains. We provide theoretical arguments how these regimes occur and interpolate among each other as one varies different parameters of the model. We also demonstrate the effect of physical dimensions (either 2D or 3D) on these regimes and argue that since in 2D the excluded volume (EV) effect is more severe compared to 3D, certain regimes do not exist in 2D. Finally, we study a model of a dsDNA , where both base-pairing and base-stacking interactions are accounted for albeit at a low computational cost compared to the other existing models. Our model correctly recovers the stiffness for dsDNA and ssDNA at different temperatures. Under most conditions of interest, a dsDNA can locally denature and form bubbles due to thermal fluctuations. At a critical temperature, a dsDNA undergoes a phase transition, in which the two strands of dsDNA completely melt to two single strands (two ssDNA). By considering EV interactions and calculating the bubble size distribution, recent studies have shown that this denaturation process is a first order transition. We show that for a homogeneous dsDNA made of only AT or GC pairs, our simulation results agree with the previous conclusion of first order transition, however, for sequences of periodic AT and GC regions, when the periodic size is relatively large compared to the sequence length, we show that the bubble size distribution exhibits peaks expressing the sequence pattern, and more importantly, the denaturation is no longer a first order transition. All these studies reported in the dissertation are relevant to the physics of living systems

Dynamics of a Charge Carrier Driven by Oscillating Fields in Materials with Impurities

In conductive materials and semiconductors, a charge carrier under the effects of an electric field will suffer collisions due to thermal fluctuations and impurities in the lattice, altering their trajectory. The electronic properties of these materials depend on the nature and frequency of these collisions; thus, they must be accounted for in any model dealing with electrical conduction. Tracking all collisions individually, while it may be possible within certain limits, forces the model to a large degree of approximation. This work introduces a Monte Carlo-based methodology to electrical transport in Ohmic materials that consists of two parts, the utilization of probability distribution functions (PDFs) for a set of collisions (coarse grain), as opposed to solving the transport equations for individual collisions and the use of homotopies to parameterize PDFs what produces a continuous set of PDFs once a relatively small number of them are explicitly parameterized. With the current approach, simulation times are from a few hundred to a few thousand times smaller than explicitly solving the transport equations. Average collision times are generated from distributions for a set of n collisions (the grain size), and from there, transport properties are calculated. Simulations were used to solve equations of motion based on the Drude’s Model of electrical conductivity. The results of the simulations are then used to generate probability distributions for various combinations of input parameters in order to coarse-grain the transport model. Grain sizes of n=5 and n=50 were considered. A homotopy on start time was first created by evaluating select distribution parameters across a half cycle. An excellent agreement non-coarse grained model was obtained.The electric field was then incorporated into the model parameterization leading to a PDF that, via a homotopy, can generate average collision time for any initial position of the carrier under any electric field within a continuous range). Results were validated using the non-coarse grained simulation under conditions not used for the parametrization for up to 500,000 collisions, with current density values being above 98.9% accurate. The goal of this work was to build a homotopy or mapping that, given some input parameters, could output some transport properties to aid experimental studies. The material of choice for this work was an ideal ohmic conductor with a mean free path of 4.3× 10−9m

Encapsulated membrane proteins: a simplified system for molecular simulation

Over the past 50 years there has been considerable progress in our understanding of biomolecular interactions at an atomic level. This in turn has allowed molecular simulation methods employing full atomistic modeling at ever larger scales to develop. However, some challenging areas still remain where there is either a lack of atomic resolution structures or where the simulation system is inherently complex. An area where both challenges are present is that of membranes containing membrane proteins. In this review we analyse a new practical approach to membrane protein study that offers a potential new route to high resolution structures and the possibility to simplify simulations. These new approaches collectively recognise that preservation of the interaction between the membrane protein and the lipid bilayer is often essential to maintain structure and function. The new methods preserve these interactions by producing nano-scale disc shaped particles that include bilayer and the chosen protein. Currently two approaches lead in this area: the MSP system that relies on peptides to stabilise the discs, and SMALPs where an amphipathic styrene maleic acid copolymer is used. Both methods greatly enable protein production and hence have the potential to accelerate atomic resolution structure determination as well as providing a simplified format for simulations of membrane protein dynamics