Nonequilibrium transport of ionic liquids in electrified nanosystems

Room-temperature ionic liquids (RTILs) are a promising class of electrolyte that are composed entirely of ions but are liquid at room temperature. Their remarkable properties such as wide electrochemical window make them ideal electrolytes in many electrochemical systems. Because the non-equilibrium transport of RTILs often determines the performance of these systems, a fundamental understanding of such transport is needed. Here, using molecular dynamic (MD) and continuum simulations, we investigated the non-equilibrium transport of RTILs in three scenarios relevant to the application of RTILs in electrochemical systems: the electroosmotic flow (EOF) of RTILs through nanochannels, the electrokinetic transport of RTILs through nanopores, and the charging kinetics of the double layers near planar electrodes. For EOFs of RTILs through nanochannels, we discovered that their strength greatly exceeds that predicted by the classical hydrodynamic theories. We traced the unexpected flow strength to the short-wavelength nature of the EOFs in RTILs, which requires the generalized hydrodynamics (i.e., nonlocal law for the shear stress-strain rate relation) for describing such flows. The EOF in RTILs is thus a rare example in which short-wavelength hydrodynamics profoundly affects flow measurables. For the electrokinetic transport of RTILs through nanopores, we discovered that, in pores wetted by RTILs a gradual dewetting transition occurs upon increasing the applied voltage, which is accompanied by a sharp increase in ionic current. These phenomena originate from the solvent-free nature of RTILs and are in stark contrast with the transport of conventional electrolytes through nanopores. Amplification of these phenomena is possible by controlling the properties of the pore and RTILs, and we showed that it is especially pronounced in charged nanopores. For the charging kinetics of the double layers near planar electrodes, we found that, the potential across the double layers can oscillate during charging when the charging current is large. Such oscillation originates from the sequential growth of the ionic space charge layers near the electrode surface. This allows the evolution of double layers in RTILs with time, an atomistic process difficult to visualize experimentally, to be studied by analyzing the cell potential under constant current charging conditions

Coarse-grained molecular dynamics of semi-flexible (bio-)polymers under force

Living organisms build upon semi-flexible biopolymers to confer structural integrity and functionality to cells. Semi-flexible (bio-)polymers assemble into hierarchical networks governed by an interplay between entropic and enthalpic effects. The assembled network features a non-linear response to mechanical load, like strain-stiffening and compression-softening. This non-linearity stems from the many-body nature at the microscale, which significantly influences the behaviour at the mesoscale. Due to the lack of non-generic scale-bridging models, the response of semi-flexible (bio-)polymer networks to mechanical stress is not yet fully understood. The aim of this thesis is thus to explore major molecular deformation mechanisms of semi-flexible (bio-)polymer networks by large-scale yet chemically informed molecular dynamics simulations. We developed coarse-grained models for two semi-flexible (bio-)polymers with similar persistence lengths, namely poly(para-phenylene ethynylene)s (PPEs) and collagen, using the Martini 3 force field to perform molecular dynamics simulations under force and to identify locations of high-force concentration with bonds being prone to rupture. Our Martini 3 models largely capture key structural, mechanical and thermodynamic observables from atomistic simulations and experiments from the literature, including interchain packing, mechanical bending stiffness and solvation properties. We show that the entanglement of PPEs in large-scale bulk assemblies increases with polymer chain length. We further observe that long-chain PPE networks under shear-flow form shear bands with extreme shear rates in the fast band, that is, where rupture forces are highest and bonds are likely to fail. Also, we built atomistic structural models for collagen microfibrils with a tuneable crosslink density and combined Martini 3 with Gō-like potentials to find an increase in microfibrillar stretching with decreasing number of crosslinks. Our Martini 3 collagen model is suited to capture the force-stretching of collagen microfibrils from all-atom simulations, performed in collaboration with the Riken institute in Kobe. The two newly developed coarse-grained models for the semi-flexible PPE and collagen complement experiments by predicting bond rupture events in the large-scale assembled polymer networks. They push the frontier of molecular dynamics simulations more close to realism, that is, to their actual biological or synthetic counterparts, and will in future allow probing micrometer sized systems of various structural configurations

Computational Techniques for Simulating the Interactions between Peptides and Carbon Nanotubes

Ph.DDOCTOR OF PHILOSOPH

Doctor of Philosophy

dissertationA theoretical study of a chemical system is focused on representing the system properly with a model and using it to accurately represent and predict physical and dynamical properties of interest. The trade off between accuracy of simulations using a theoretical model and its computational expense is an important consideration in choosing and implementing the model and accompanying force field. My research has sampled the two extremes of this balance. In developing the mW-Ion and mW/3SPNDNA models, a coarse-grained technique was used to simplify the interactions and significantly increase the efficiency of the calculations with respect to atomistic simulations. These models have limited transferability to other studies due to their coarseness, but reproduce properties such as solvation structure and ion dynamics quite well, and this with the ability to extend the simulation studies to timescales intractable for their atomistic counterparts. In later work, while investigating potential improvements to solid polymer electrolytes used in lithium battery technologies, an atomistic model with a polarizable force field was used in order to correctly capture the mobility of lithium cations. This involved a considerably larger computational expense, but was necessary to retain fidelity to experimental data. The advantages and disadvantages of the two sides of this balance is explored here, with detailed examination of the models and force fields used, their applicability, and broader impact in the simulation and scientific community

Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

Cells are strongly out-of-equilibrium systems driven by continuous energy supply. They carry out many vital functions requiring active transport of various ingredients and organelles, some being small, others being large. The cytoskeleton, composed of three types of filaments, determines the shape of the cell and plays a role in cell motion. It also serves as a road network for the so-called cytoskeletal motors. These molecules can attach to a cytoskeletal filament, perform directed motion, possibly carrying along some cargo, and then detach. It is a central issue to understand how intracellular transport driven by molecular motors is regulated, in particular because its breakdown is one of the signatures of some neuronal diseases like the Alzheimer. We give a survey of the current knowledge on microtubule based intracellular transport. We first review some biological facts obtained from experiments, and present some modeling attempts based on cellular automata. We start with background knowledge on the original and variants of the TASEP (Totally Asymmetric Simple Exclusion Process), before turning to more application oriented models. After addressing microtubule based transport in general, with a focus on in vitro experiments, and on cooperative effects in the transportation of large cargos by multiple motors, we concentrate on axonal transport, because of its relevance for neuronal diseases. It is a challenge to understand how this transport is organized, given that it takes place in a confined environment and that several types of motors moving in opposite directions are involved. We review several features that could contribute to the efficiency of this transport, including the role of motor-motor interactions and of the dynamics of the underlying microtubule network. Finally, we discuss some still open questions.Comment: 74 pages, 43 figure

Nonlocal Models in Biology and Life Sciences: Sources, Developments, and Applications

Nonlocality is important in realistic mathematical models of physical and biological systems at small-length scales. It characterizes the properties of two individuals located in different locations. This review illustrates different nonlocal mathematical models applied to biology and life sciences. The major focus has been given to sources, developments, and applications of such models. Among other things, a systematic discussion has been provided for the conditions of pattern formations in biological systems of population dynamics. Special attention has also been given to nonlocal interactions on networks, network coupling and integration, including models for brain dynamics that provide us with an important tool to better understand neurodegenerative diseases. In addition, we have discussed nonlocal modelling approaches for cancer stem cells and tumor cells that are widely applied in the cell migration processes, growth, and avascular tumors in any organ. Furthermore, the discussed nonlocal continuum models can go sufficiently smaller scales applied to nanotechnology to build biosensors to sense biomaterial and its concentration. Piezoelectric and other smart materials are among them, and these devices are becoming increasingly important in the digital and physical world that is intrinsically interconnected with biological systems. Additionally, we have reviewed a nonlocal theory of peridynamics, which deals with continuous and discrete media and applies to model the relationship between fracture and healing in cortical bone, tissue growth and shrinkage, and other areas increasingly important in biomedical and bioengineering applications. Finally, we provided a comprehensive summary of emerging trends and highlighted future directions in this rapidly expanding field.Comment: 71 page

ENGINEERING DNA-BASED NANOCHANNELS AND VESICLES FOR CONTROLLED MOLECULAR TRANSPORT

For the past two decades, synthetic transmembrane nanopores and nanochannels have become powerful tools in biosensing and single-molecule studies. Due to the ease of rational design and advancements in DNA functionalization, DNA has been established to be versatile building blocks for the bottom-up fabrication of nanostructures. Recently, DNA-based nanopores in both small diameters (1-2 nm) showing transport of ions and small molecules and large diameters (5-10 nm) showing transport of proteins across lipid bilayer membranes were reported. Nevertheless, those DNA nanopores have lengths below 100 nm, and the molecular transport only occurs across lipid membranes. It remains unknown if longer nanochannels can be constructed for transport over extended distances. Such nanochannels of longer lengths can be potentially used as conduits for carrying molecules on the cell-size scale or between compartments apart. We have designed a microns-long DNA nanochannel 7 nm inner diameter that inserts onto the lipid membranes of giant unilamellar vesicles and allows the transport of small molecules through its barrel. Kinetics analysis suggests a continuum diffusion model can describe the transport phenomenon within the DNA nanochannel. The reduced transport upon bindings of DNA origami caps to the channel ends reveals the molecules mainly transport from one channel end to the other rather than leak across channel walls. We further design a DNA nanopore-cap system that responds to specific DNA sequences. In combination with giant unilamellar vesicles that encapsulate glucose molecules, we present a biosensor system consisting of capped DNA nanopores and vesicles that can detect and amplify nanomolar DNA signals millimolar glucose outputs. The DNA-based biosensor we developed shows the potentials to be used as point-of-care nucleic acid diagnostic devices. Another challenge in using DNA nanochannels or other DNA-based nanostructures in biological environments or cell culture is that they may be degraded by enzymes found in these environments, such as nucleases. To improve the DNA nanostructures' stability, we demonstrate a means by which degradation can be reversed in situ through the repair of nanostructure defects. The ability to repair nanostructures, such as DNA nanochannels, could allow particular structures or devices to operate for long periods of time and might offer a single means to resist different types of chemical degradation

Bio-Nano Robo-Mofos : Design and Synthesis of DNA Origami Nanostructures and Assembly of Nanobot Superstructures

In the field of bio-nanotechnology, molecules like DNA are repurposed as building materials for the construction of self-assembling nanostructures. The DNA origami method involves rationally coding many short synthetic DNA strands which ‘fold’ longer scaffold strands into precise, addressable structures for applications in areas like medicine, structural biology and molecular biophysics. DNA origami subunits are also used to explore fundamental principles of self-assembly, revealing insights into biology and expanding our control of matter at the nanoscale. But despite the usefulness of the method, DNA origami designs are limited in size by the length of scaffold strands, and in scope by the available tools needed to navigate the complex geometries of DNA nanostructures. My thesis addresses this in two ways: First, I present a set of principles for the design of DNA origami nanotubes, a class of strained structure with many applications. I parametrised variables related to nanotube design and created a computational tool to convert desired geometries into DNA strand layouts. I validated this via synthesis of various designs, including novel nanotubes with pleated walls, reconfigurable twist and varying diameter, characterising them with TEM, SAXS and MD simulations. This revealed insights into how design variables affect properties such as diameter and rigidity, and how global strain affects DNA nanostructures. Next, I present two schemes for assembling DNA origami subunits into self-limiting, open superstructures, exploring fundamental principles to control self-assembly while also overcoming DNA origami’s size limitations. The first is a strain accumulation scheme, which was explored theoretically and then embodied in a modular subunit with allosteric binding domains. With simulation and synthesis, I demonstrated that the subunit could structurally encode the extent of its own polymerisation. The second scheme is Vernier assembly, in which I showed that the combined geometries of two DNA origami subunits could determine the size of a superstructure and explored parameters important to maximise yield. Both studies provide guidance for future studies and applications which may require finite superstructures made from small numbers of unique components. Combined, the works in this thesis expand the design space for DNA-nanotechnology and fields beyond, enabling a range of biologically-inspired nanoscale autonomous modular formations, or ‘Bio-Nano Robo-Mofos’