In the living cell, the organization of the complex internal structure relies to a large extent on molecular motors. Molecular motors are proteins that are able to convert chemical energy from the hydrolysis of adenosine triphosphate (ATP) into mechanical work. Being about 10 to 100 nanometers in size, the molecules act on a length scale, for which thermal collisions have a considerable impact onto their motion. In this way, they constitute paradigmatic examples of thermodynamic machines out of equilibrium. This study develops a theoretical description for the energy conversion by the molecular motor myosin V, using many different aspects of theoretical physics. Myosin V has been studied extensively in both bulk and single molecule experiments. Its stepping velocity has been characterized as a function of external control parameters such as nucleotide concentration and applied forces. In addition, numerous kinetic rates involved in the enzymatic reaction of the molecule have been determined. For forces that exceed the stall force of the motor, myosin V exhibits a 'ratcheting' behaviour: For loads in the direction of forward stepping, the velocity depends on the concentration of ATP, while for backward loads there is no such influence. Based on the chemical states of the motor, we construct a general network theory that incorporates experimental observations about the stepping behaviour of myosin V. The motor's motion is captured through the network description supplemented by a Markov process to describe the motor dynamics. This approach has the advantage of directly addressing the chemical kinetics of the molecule, and treating the mechanical and chemical processes on equal grounds. We utilize constraints arising from nonequilibrium thermodynamics to determine motor parameters and demonstrate that the motor behaviour is governed by several chemomechanical motor cycles. In addition, we investigate the functional dependence of stepping rates on force by deducing the motor's response to external loads via an appropriate Fokker-Planck equation. For substall forces, the dominant pathway of the motor network is profoundly different from the one for superstall forces, which leads to a stepping behaviour that is in agreement with the experimental observations. The extension of our analysis to Markov processes with absorbing boundaries allows for the calculation of the motor's dwell time distributions. These reveal aspects of the coordination of the motor's heads and contain direct information about the backsteps of the motor. Our theory provides a unified description for the myosin V motor as studied in single motor experiments.

Presenting a state-of-the-art overview of theoretical and computational models that link characteristic biomechanical phenomena, this book provides guidelines and examples for creating multiscale models in representative systems and organisms. It develops the reader's understanding of and intuition for multiscale phenomena in biomechanics and mechanobiology, and introduces a mathematical framework and computational techniques paramount to creating predictive multiscale models. Biomechanics involves the study of the interactions of physical forces with biological systems at all scales – including molecular, cellular, tissue and organ scales. The emerging field of mechanobiology focuses on the way that cells produce and respond to mechanical forces – bridging the science of mechanics with the disciplines of genetics and molecular biology. Linking disparate spatial and temporal scales using computational techniques is emerging as a key concept in investigating some of the complex problems underlying these disciplines. Providing an invaluable field manual for graduate students and researchers of theoretical and computational modelling in biology, this book is also intended for readers interested in biomedical engineering, applied mechanics and mathematical biology.

This volume examines a number of different molecular motors that utilize ATP. The molecular machines to be discussed include ATP synthase, myosin, kinesin, DNA helicases, DNA topoisomerases, chaperones and bacterial rotory motors. The discussion of these various molecular motors is rarely undertaken in one volume and will serve as a great resource for scientists studying structure and function of multiprotein complexes as well as those working on energy coupling mechanisms. The areas of research presented in this volume do not normally overlap, and yet they share common mechanisms. This volume examines a number of different molecular motors that utilize ATP. The molecular machines to be discussed include ATP synthase, myosin, kinesin, DNA helicases, DNA topoisomerases, chaperones and bacterial rotory motors. The discussion of these various molecular motors is rarely undertaken in one volume and will serve as a great resource for scientists studying structure and function of multiprotein complexes as well as those working on energy coupling mechanisms. The areas of research presented in this volume do not normally overlap, and yet they share common mechanisms.

The latest knowledge on molecular motors is vital for the understanding of a wide range of biological and medical topics: cell motility, organelle movement, virus transport, developmental asymmetry, myopathies, and sensory defects are all related to the function or malfunction of these minute molecular machines. Since there is a vast amount of information on motor mechanisms and potential biomedical and nanobiotechnological applications, this handbook fulfills the need for a collection of current research results on the functionality, regulation, and interactions of cytoskeletal, DNA, and rotary motors. Here, leading experts present a concise insight, ranging from atomic structure, biochemistry, and biophysics to cell biology, developmental biology and pathology. Basic principles and applications make this book a valuable reference tool for researchers, professionals, and clinicians alike - all set to become a "classic" in the years to come.

This highly authoritative volume highlights the remarkable superfamily of molecular motors called myosins, which are involved in such diverse cellular functions as muscle contraction, intracellular transport, cell migration and cell division. In a timely compilation of chapters written by leading research groups that have made key discoveries in the field, the current understanding of the molecular mechanisms and biological functions of these intriguing proteins is explored.

This book will contain a series of solicited chapters that concern with the molecular machines required by viruses to perform various essential functions of virus life cycle. The first three chapters (Introduction, Molecular Machines and Virus Architecture) introduce the reader to the best known molecular machines and to the structure of viruses. The remainder of the book will examine in detail various stages of the viral life cycle. Beginning with the viral entry into a host cell, the book takes the reader through replication of the genome, synthesis and assembly of viral structural components, genome packaging and maturation into an infectious virion. Each chapter will describe the components of the respective machine in molecular or atomic detail, genetic and biochemical analyses, and mechanism. Topics are carefully selected so that the reader is exposed to systems where there is a substantial infusion of new knowledge in recent years, which greatly elevated the fundamental mechanistic understanding of the respective molecular machine. The authors will be encouraged to simplify the detailed knowledge to basic concepts, include provocative new ideas, as well as design colorful graphics, thus making the cutting-edge information accessible to broad audience.

Myosin V is a double-headed molecular motor that moves processively along actin filaments. Its processivity requires coordination between its two heads to keep their ATPase cycles out of phase, preventing both heads from detaching actin simultaneously. However, the kinetic scheme that two-headed myosin V takes during its processive run has long been debated. To address this issue, we studied the processivity (velocity and run length) of myosin V at multiple substrate conditions under zero load. We found that increasing [ATP] decreased the run length of myosin V, and a high phosphate concentration in the solution decreased both velocity and run length, as well as marlcedly increased the ratio of backsteps. Theses results are well explained by a lunetic model (Baker et al., 2004) in which myosin V proceeds through a branched kinetic pathway.