Transmembrane molecular machines

Transmembrane molecular machines are ubiquitous in nature. These evolved systems demonstrate superlative elegance and efficiency of operation. Imitation and hijacking of biological components such as proteins and DNA has emerged as a means of imparting desirable characteristics to rationally designed synthetic molecular machines. This thesis presents work towards various synthetic transmembrane molecular machines based on alpha-haemolysin (α-HL). Chapter One reviews progress towards synthetic transmembrane machines, introducing natural examples, defining criteria for being ‘a molecular machine’ cataloguing examples and trends in synthetic molecular machines in solution, on surfaces and in membranes. Examples are evaluated in terms of their machine like behaviour and α-HL emerges as a particularly promising component in the development of synthetic transmembrane molecular machines. Chapter Two examines solvent isotope effects resulting from substitution of hydrogen by deuterium in water at the nanoscale – on the rates of transmembrane ion transport and transmembrane translocation of ssDNA through α-HL, both of which are of concern in the context of building molecular machines which use α-HL as a component. Chapters Three to Six look at different machine applications of related transmembrane architectures based on individual transmembrane rotaxanes constructed in α-HL from DNA/PEG copolymer ‘thread’ strands and DNA ‘primer’ strands. Chapter Three uses this approach to observe translational motion of the thread strand in both directions along the z-axis due to nucleotide incorporation and pyrophosphorolysis in real-time with single-nucleotide resolution. Chapter Four provides the first demonstration of asymmetrical, hysteretic cyclical behaviour in the translational motion of the thread strand by incorporation of a nicking site which resets the system after nucleotide incorporations have occurred. Chapter Five introduces a novel variant of the rotaxane architecture using a circularised primer strand which allows real time observation of rolling circle amplification at the single molecule level by coupling the process to the unidirectional translocation of the thread strand. Chapter Six considers the use of the vestibule of α-HL as a transmembrane DNA ligase mimic with the DNA thread/primer complex as substrate

Roadmap on semiconductor-cell biointerfaces.

This roadmap outlines the role semiconductor-based materials play in understanding the complex biophysical dynamics at multiple length scales, as well as the design and implementation of next-generation electronic, optoelectronic, and mechanical devices for biointerfaces. The roadmap emphasizes the advantages of semiconductor building blocks in interfacing, monitoring, and manipulating the activity of biological components, and discusses the possibility of using active semiconductor-cell interfaces for discovering new signaling processes in the biological world

Advances Towards Synthetic Machines at the Molecular and Nanoscale Level

The fabrication of increasingly smaller machines to the nanometer scale can be achieved by either a “top-down” or “bottom-up” approach. While the former is reaching its limits of resolution, the latter is showing promise for the assembly of molecular components, in a comparable approach to natural systems, to produce functioning ensembles in a controlled and predetermined manner. In this review we focus on recent progress in molecular systems that act as molecular machine prototypes such as switches, motors, vehicles and logic operators

Self-Organization at the Nanoscale Scale in Far-From-Equilibrium Surface Reactions and Copolymerizations

An overview is given of theoretical progress on self-organization at the nanoscale in reactive systems of heterogeneous catalysis observed by field emission microscopy techniques and at the molecular scale in copolymerization processes. The results are presented in the perspective of recent advances in nonequilibrium thermodynamics and statistical mechanics, allowing us to understand how nanosystems driven away from equilibrium can manifest directionality and dynamical order.Comment: A. S. Mikhailov and G. Ertl, Editors, Proceedings of the International Conference "Engineering of Chemical Complexity", Berlin Center for Studies of Complex Chemical Systems, 4-8 July 201