Neuronal Mechanics and Transport


Book Description

Understanding the underlying mechanisms of how axons and dendrites develop is a fundamental problem in neuroscience and a main goal of research on nervous system development and regeneration. Previous studies have provided a tremendous amount of information on signaling and cytoskeletal proteins regulating axonal and dendritic growth and guidance. However, relatively little is known about the relative contribution and role of cytoskeletal dynamics, transport of organelles and cytoskeletal components, and force generation to axonal elongation. Advancing the knowledge of these biomechanical processes is critical to better understand the development of the nervous system, the pathological progression of neurodegenerative diseases, acute traumatic injury, and for designing novel approaches to promote neuronal regeneration following disease, stroke, or trauma. Mechanical properties and forces shape the development of the nervous system from the cellular up to the organ level. Recent advances in quantitative live cell imaging, biophysical, and nanotechnological methods such as traction force microscopy, optical tweezers, and atomic force microscopy have enabled researchers to gain better insights into how cytoskeletal dynamics and motor-driven transport, membrane-dynamics, adhesion, and substrate rigidity influence axonal elongation. Given the complexity and mechanical nature of this problem, mathematical modeling contributes significantly to our understanding of neuronal mechanics. Nonetheless, there has been limited direct interaction and discussions between experimentalists and theoreticians in this research area. The purpose of this Frontiers Research Topic is to highlight exciting, and important work that is currently developing in the fields of neuronal cell biology, neuronal mechanics, intracellular transport, and mathematical modeling in the form of primary research articles, reviews, perspectives, and commentaries.




Neuronal Mechanics and Transport


Book Description

Understanding the underlying mechanisms of how axons and dendrites develop is a fundamental problem in neuroscience and a main goal of research on nervous system development and regeneration. Previous studies have provided a tremendous amount of information on signaling and cytoskeletal proteins regulating axonal and dendritic growth and guidance. However, relatively little is known about the relative contribution and role of cytoskeletal dynamics, transport of organelles and cytoskeletal components, and force generation to axonal elongation. Advancing the knowledge of these biomechanical processes is critical to better understand the development of the nervous system, the pathological progression of neurodegenerative diseases, acute traumatic injury, and for designing novel approaches to promote neuronal regeneration following disease, stroke, or trauma. Mechanical properties and forces shape the development of the nervous system from the cellular up to the organ level. Recent advances in quantitative live cell imaging, biophysical, and nanotechnological methods such as traction force microscopy, optical tweezers, and atomic force microscopy have enabled researchers to gain better insights into how cytoskeletal dynamics and motor-driven transport, membrane-dynamics, adhesion, and substrate rigidity influence axonal elongation. Given the complexity and mechanical nature of this problem, mathematical modeling contributes significantly to our understanding of neuronal mechanics. Nonetheless, there has been limited direct interaction and discussions between experimentalists and theoreticians in this research area. The purpose of this Frontiers Research Topic is to highlight exciting and important work that is currently developing in the fields of neuronal cell biology, neuronal mechanics, intracellular transport, and mathematical modeling in the form of primary research articles, reviews, perspectives, and commentaries.




A Quantitative Study of the Axonal Transport Mechanics in Neurons


Book Description

Neurons are highly polarized cells with their axon often extending over large distances away from the cell bodies (up to 1 meter in axonal length with a cell body less than 50 micrometer in diameter). Given that the majority of neuronal proteins and materials are synthesized in the cell body, such a long axon precludes effective diffusion of soma-produced proteins to their presynaptic destinations at the axonal terminals. As a result, neurons rely extensively on active axonal transport to deliver newly synthesized synaptic proteins, ion channels, lipids, and mitochondria to their axonal destinations via anterograde transport. On the other hand, retrograde axonal transport is responsible for carrying molecules and organelles destined for degradation from the axonal terminals back to the cell body. A highly efficient and tightly regulated machinery is thus required for a robust long-range transport of materials to ensure the neurons' proper growth, maintenance and survival. This thesis is a quantitative study of the underlying mechanism of axonal transport, with a specific focus on the retrograde axonal transport machinery in neurons. In our experimental setup, the axonal transport of cargos can be directly visualized in real-time using a neuronal microfluidic platform and fluorescence microscopy technique. We observe that cargos have high tendency to slow down their transport speed when crossing various obstacles along the axon such as non-moving cargos and stationary mitochondria. Single molecule study of retrograde nerve growth factor transport reveals that mechanical tug-of-war and intracellular motor regulation are complementary features of the near-unidirectional endosome directionality. Specifically, a stochastic mechanical simulation suggests that the endosomes are driven on average by 5-6 active dyneins and 1-2 down-regulated kinesins. This result is further supported by a study of the dynamics of endosomes detaching under load in axons, showcasing the cooperativity of multiple dyneins and the subdued activity of kinesins. Lastly, we present a quantitative characterization of the complex behavior of light-sensitive cryptochrome 2 (CRY2) protein under blue light. The results contribute to the understanding of the light-inducible CRY2 system and can be used as a guide to establish new optogenetic strategies to probe cellular processes in live cells.




Transport Phenomena in the Nervous System


Book Description

It is more recently becoming increasingly clear, however, that the homeostatic equilibrium, and its physiological and pathological changes, are governed by a complex set of mechanisms residing heterogeneously in a complex set of membranes. Mechanisms residing in the capillary endothelium are of importance - especially in short term penetration studies of administered substances from blood to brain; the physiological and pathological equilibria are likely to be more influenced and governed by mechanisms residing in neuronal, glial, nuclear, and lysosomal membranes, to name a few. For functional importance in turn, mechanisms residing in mitochondrial and synaptosomal membranes are of crucial importance, for transport out of the system those present in choroid plexus among others have to be studied.







Axonal Transport in Neuronal Growth and Regeneration


Book Description

Over the past several years, the pace of research on the control of axonal growth has increased at a remarkable rate, and this activity is reflected in a growing literature dealing with various aspects of axonal growth and regener ation. It appears timely to review the role played by axonal transport in the intrinsic responses of neurons in the growth and regrowth processes. Through the cooperation of the senior editors of this series, we have been given the opportunity to bring such a focus to the current volume. We wish to acknowledge that the contributing authors attended a confer ence on "The Role of Axonal Transport in Neuronal Growth and Regenera tion" held in Tallahassee, Florida in March, 1983, sponsored by the Psycho biology Research Center of the Florida State University. It is our hope that many of the perceptions and insights expressed in these chapters resulted from our interactions.




Nano and Cell Mechanics


Book Description

Research in nano and cell mechanics has received much attention from the scientific community as a result of society needs and government initiatives to accelerate developments in materials, manufacturing, electronics, medicine and healthcare, energy, and the environment. Engineers and scientists are currently engaging in increasingly complex scientific problems that require interdisciplinary approaches. In this regard, studies in this field draw from fundamentals in atomistic scale phenomena, biology, statistical and continuum mechanics, and multiscale modeling and experimentation. As a result, contributions in these areas are spread over a large number of specialized journals, which prompted the Editors to assemble this book. Nano and Cell Mechanics: Fundamentals and Frontiers brings together many of the new developments in the field for the first time, and covers fundamentals and frontiers in mechanics to accelerate developments in nano- and bio-technologies. Key features: • Provides an overview of recent advances in nano and cell mechanics. • Covers experimental, analytical, and computational tools used to investigate biological and nanoscale phenomena. • Covers fundamentals and frontiers in mechanics to accelerate developments in nano- and bio-technologies. • Presents multiscale-multiphysics modeling and experimentation techniques. • Examines applications in materials, manufacturing, electronics, medicine and healthcare. Nano and Cell Mechanics: Fundamentals and Frontiers is written by internationally recognized experts in theoretical and applied mechanics, applied physics, chemistry, and biology. It is an invaluable reference for graduate students of nano- and bio-technologies, researchers in academia and industry who are working in nano and cell mechanics, and practitioners who are interested in learning about the latest analysis tools. The book can also serve as a text for graduate courses in theoretical and applied mechanics, mechanical engineering, materials science, and applied physics.




Protein Trafficking in Neurons


Book Description

The efficient delivery of cellular constituents to their proper location is of fundamental importance for all cells and is of particular interest to neuroscientists, because of the unique functions and complex architecture of neurons. Protein Trafficking in Neurons examines mechanisms of protein trafficking and the role of trafficking in neuronal functioning from development to plasticity to disease. The book is divided into seven sections that review mechanisms of protein transport, the role of protein trafficking in synapse formation, exo- and endocytosis, transport of receptors, trafficking of ion channels and transporters, comparison of trafficking mechanisms in neuronal vs. non-neuronal cell types, and the relationship between trafficking and neuronal diseases such as Alzheimer's, Huntington's and Prion Diseases. - Provides a comprehensive examination of membrane/protein movement in neuronal function - Sections on synapse development, synaptic transmission, and the role of trafficking in neurological disease - Includes a focus on Molecular Mechanisms - Illustrated with color summary pictures - The only book examining protein trafficking and its functional implications, written by leaders in the field




Axonal Transport


Book Description

This volume covers a wide range of model systems from invertebrate to humans and in vitro and in vivo. Chapters detail methods on squid, aplysia, xenopus, mouse in vivo, ex vivo, rodent primary neurons, human-derived neurons, zebrafish, drosophila in vivo, primary neurons, c. elegans, and in vitro reconstitution assays.Written in the format of the highly successful Methods in Molecular Biology series, each chapter includes an introduction to the topic, lists necessary materials and reagents, includes tips on troubleshooting and known pitfalls, and step-by-step, readily reproducible protocols. Authoritative and cutting-edge, Axonal Transport: Methods and Protocols aims to further our understanding of the trafficking of cellular components in the nervous system leading to the advancement of basic knowledge that underlines the cell biology of the neuron. The chapters “ Live imaging of RNA Transport and Translation in Xenopus Retinal Axons, Retrograde Axonal Transport of Neurotrophins in Basal Forebrain Cholinergic Neurons, Assessment of Mitochondrial Trafficking as A Surrogate of Fast Axonal Transport in Human Induced Pluripotent Stem Cell Derived Spinal Motor Neurons, Drosophila Primary Neuronal Cultures as a Useful Cellular Model to Study and Image Axonal Transport, and In vitro Reconstitution of Kinesin-Based, Axonal mRNA Transport” are available open access under a Creative Commons Attribution 4.0 International License via link.springer.com