Giving Metamaterials a Hand

The focus of this thesis is the interaction of electromagnetic fields with chiral structures in the microwave regime. Through this study, which focuses on three regimes of electromagnetic interactions, I aim to develop a deeper understanding of the consequences and manifestations of chiral interactions The structures are on the order of, or smaller than, the wavelength of the probing radiation. As the structures are chiral, they have broken inversion symmetry, and exist in two states where one is the mirror image of the other. The results in this thesis can have impacts on future optical communications technologies and methods of sensing biological molecules. To begin with, the manipulation of the circular polarisation of a propagating beam by bilayer chiral metasurfaces is investigated. The metasurfaces consist of two layers of stacked crosses with a twist between top and bottom layers, forming chiral metamolecules. A broad frequency region of dispersionless polarisation rotation appears between two resonances, due to alignment between electric and magnetic dipoles. The dependence of this effect on the layer separation is studied for two similar metasurfaces. Evanescent chiral electromagnetic fields are the focus of the next chapter. An array of chiral antennas produces chiral near-fields at their resonant frequency. Aligned and subwavelength helices placed within this field interact differently depending on the handedness of the field with respect to the handedness of the helices. This difference in interaction strength is measured for the helices and an effective medium model where multipolar interactions are forbidden. Comparison of these two systems leads to the conclusion that the contribution to a chiral interaction from multipolar modes is minimal, in contrast to previous publications. The third study concentrates on the electromagnetic wave bound to an "infinitely long" metal helix. The helix has infinite-fold screw symmetry, and this leads to interesting features in the energy-dispersion of the waves it supports. The broad frequency range of high, tunable, dispersionless index is interpreted using a geometrical approach, and the factors that limit the bandwidth explained. A modified geometry is suggested for increased bandwidth. The final part of the thesis is dedicated to future work, based on the results presented thus far. Three suggestions for future study are presented, including chiroptical signals from higher-order chiral arrangements, the effect of reflecting surfaces next to chiral objects and the possible use of orbital angular momentum for chiroptical measurements.Engineering and Physical Sciences Research Council (EPSRC

Introduction to protein folding for physicists

The prediction of the three-dimensional native structure of proteins from the knowledge of their amino acid sequence, known as the protein folding problem, is one of the most important yet unsolved issues of modern science. Since the conformational behaviour of flexible molecules is nothing more than a complex physical problem, increasingly more physicists are moving into the study of protein systems, bringing with them powerful mathematical and computational tools, as well as the sharp intuition and deep images inherent to the physics discipline. This work attempts to facilitate the first steps of such a transition. In order to achieve this goal, we provide an exhaustive account of the reasons underlying the protein folding problem enormous relevance and summarize the present-day status of the methods aimed to solving it. We also provide an introduction to the particular structure of these biological heteropolymers, and we physically define the problem stating the assumptions behind this (commonly implicit) definition. Finally, we review the 'special flavor' of statistical mechanics that is typically used to study the astronomically large phase spaces of macromolecules. Throughout the whole work, much material that is found scattered in the literature has been put together here to improve comprehension and to serve as a handy reference.Comment: 53 pages, 18 figures, the figures are at a low resolution due to arXiv restrictions, for high-res figures, go to http://www.pabloechenique.co

Deterministic and stochastic dynamics in bacterial systems

Microorganisms form an essential part of our biosphere and represent roughly 14 percent of the biomass on earth. In spite of this abundance, the majority of chemical and physical processes governing the live of microorganisms remain poorly understood. In this work, we focus on three different phenomena from the realm of microorganisms and aim to explain the physical processes behind them. We examine how the bacterium Shewanella Putrefaciens exploits a mechanical instability to wrap its flagellum around its cell body, effectively forming a screw that allows the bacterium to escape from traps. Based on a numerical model we study the onset of screw formation in dependence of the flagellar geometry and the existence of multiple equilibrium configurations of the flagellum. Furthermore, we study the effects of actively swimming microorganisms on the diffusion of passive tracer particles. By means of a numerical simulation we examine a single swimmer-tracer interaction and use the results to develop a model based on continuous time random walks that captures a series of swimmer-tracer interactions. We derive an analytical expression for the one dimensional probability density function of the tracer displacements and use numerical simulations to approximate the two- and three-dimensional distributions. We then extend the model to include periods of free tracer diffusion between the tracerswimmer interactions and fit this extended model to a number of experimentally observed tracer distributions. In the third part of this work we examine how the cylindrical shape of a bacterium affects the isotropic trajectories of membrane proteins when observed with a microscope. We derive an analytical expression for the anisotropic distribution of the particle displacements when projected in the observation plane and use this result to calculate the mean squared displacement curves. Finally, we use numerical simulations to study the effects of a limited focus depth and to understand the resulting challenges for the estimation of the diffusion coefficients

Plasmonic spectroscopy of biomacromolecules with chiral metamaterial

This thesis explores the applications of injection-moulded chiral plasmonic nanostructures for biomolecules sensing. Such nanostructures enhance the chiroptical signal generated by chiral objects with plasmonic fields. These fields can produce a greater asymmetry than circularly polarised light and are called “Superchiral” fields. They are a very efficient tool for the detection of higher order structures (tertiary, quaternary) in proteins. Subsequently plasmonic metamaterials used for sensing will be introduced. We will demonstrate that the chiral fields they generate, are sensitive to the orientation of the biomolecular material at the surface and the conformation of biomolecular complexes, and that they can sense highly symmetrical structures such as viruses. In the first results chapter it will be shown that the chiral fields are highly sensitive to the surface charges of a protein. It will be shown that the surface charges of the analyte can enhance or reduce the chiral fields depending on the handedness of the fields and the state of charge of the analyte. This new property of the chiral structures leads to several applications in biology. This effect is characterised by a new type of asymmetry in the optical rotatory dispersion (ORD) spectra, thus a new asymmetry parameter will be introduced. This offers a route to rapid determination of the isoelectric points of proteins without prior knowledge of their primary sequences. It can also help to predict protein solubility in solution, their folding and interactions with other biomolecules. The new asymmetry parameter will be shown to be sensitive to the geometry of protein-protein complexes and therefore to the specificity of an interaction between two proteins. Non-specific interaction leads to isotropic complexes and hence gives a weak chiroptical signal. It is also explained that the new asymmetry parameter, introduced in the first results chapter, is a good indicator of the order of the analyte at the metafilm surface. Furthermore, we will show that this sensitivity for surface charges allows the detection of highly symmetrical biomolecules such as plant viruses. The fingerprint in the ORD for viruses with the same geometry and same size but different isoelectric points is shown to be dissimilar. Another property of the nanostructures is the ability to display plasmonic induced transparency (PIT). The model of the PIT allows the asymmetry to be measured in the phase retardation. This parameter ΔΔφ is shown to be more sensitive to surface charges and hence allows higher accuracy in virus detection. Chiral fields are also efficient in distinguishing between virions and virus-like particles (VLP). The effect of adding a gold binding domain on the virus particles is explored, and proved efficient, even though the chemistry of the virus surface is changed. Finally, chiral fields are used to sense rod-shaped viruses. This chapter emphasizes the sensitivity of the parameters ΔΔφ and raises the problem of the sensitivity limit for bigger macromolecules. The effect on the asymmetry is shown to be dependent on the orientation of the particles. Using the chirality tensor, the detection limit of macro-biomolecules in the chiral fields will be described

Modelling the Effects of Disease-Associated Single Amino Acid Variants and Rescuing the Effects by Small Molecules

Single nucleotide polymorphism (SNP) is a variation of a single nucleotide in the genome. Some of these variations can cause a change of single amino acid in the corresponding protein, resulting in single amino acid variation (SAV). SAVs can lead to profound alterations of the corresponding biological processes and thus can be associated with many human diseases. This dissertation focuses on integration of existing and development of new computational approaches to model the effects of SAVs with the goal to reveal molecular mechanism of human diseases. Since proton transfer and pKa shifts are frequently attributed to disease causality, the proton transfers in the protein-nucleic acid interactions are investigated and along with development of a new computational approach to predict the SAV’s effect on the protein-DNA binding affinity. The SAVs in four proteins: Lysine-specific demethylase 5C (KDM5C), Spermine Synthase (SpmSyn), 7-Dehydrocholesterol reductase (DHCR7) and methyl CpG binding protein 2 (MeCP2) are extensively studied using numerous computational approaches to reveal molecular details of disease-associated effects. In case of MeCP2 protein, the effects of the most commonly occurring disease-causing mutation, R133C, was targeted by structure-based virtual screening to identify the small molecules potentially to rescue the malfunctioning R133C mutant