Genetically Tuning Cellular Mechanobiology
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Genetically Tuning Cellular Mechanobiology
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Author : Joanna Lynn MacKay
language : en
Publisher:
Release Date : 2013
Genetically Tuning Cellular Mechanobiology written by Joanna Lynn MacKay and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2013 with categories.
The recognition that cells can sense physical cues has inspired numerous investigations into the roles that mechanical forces play in both healthy and diseased cells. This rapidly growing area of research, often called cellular mechanobiology, has shown that physical interactions between cells and the surrounding extracellular matrix can regulate a number of fundamental cell behaviors. This insight has prompted the development of new methods to systematically engineer the mechanical properties of extracellular matrices (e.g., rigidity and geometry), both as a way to study the mechanisms behind cellular mechanosensing and as a way to directly control cell behavior in tissue engineering applications. In contrast, an equally powerful approach for manipulating cell-matrix interactions could be to directly engineer the mechanical properties of the cells themselves by modifying the intracellular signaling pathways that regulate how cells sense and respond to physical cues. This type of "inside-out" strategy would be useful for controlling cell behavior independently from extracellular matrix properties and would allow investigation into how changes in cellular mechanics such as cell shape, stiffness, and contractility can directly alter cell behavior. In these dissertation studies, a genetic strategy was developed to precisely control the mechanical properties and motility of cells by manipulating the activity of cytoskeletal signaling proteins. Genetic mutants of the signaling proteins RhoA GTPase, Rac1 GTPase, or myosin light chain kinase (MLCK) were introduced into human glioblastoma cells under the control of conditional promoters, thereby enabling graded and dynamic control over their expression through addition and withdrawal of the transcriptional inducers. Increasing the activity of RhoA or MLCK by inducibly expressing constitutively active (CA) mutants increased both the stiffness and the contractility of cells in a graded manner, which had an inhibitory effect on cell migration. Interestingly, decreasing RhoA activity through expression of a dominant negative (DN) mutant also produced a graded decrease in cell migration speed, indicating that cell motility varies biphasically with RhoA activity levels. A similar biphasic dependence was discovered upon varying the activity of Rac1. These results demonstrate the importance of using quantitative methods to reveal potentially nonlinear relationships between protein activity and cell behavior. Expanding upon this strategy, two orthogonal promoter systems were combined to provide simultaneous control over the activity of two proteins in the same cell. RhoA and Rac1 are known to suppress each other through crosstalk between their signaling pathways, suggesting that cells can normally have high activity of only one protein or the other. To investigate the effects of forcing high activation of both proteins, CA RhoA and CA Rac1 were introduced into the same cells under different conditional promoters (either doxycycline-inducible or cumate-inducible). Expression of CA RhoA did not alter Rac1 activity and vice versa, demonstrating that the activity levels of RhoA and Rac1 can be independently varied with this strategy. Notably, expressing both CA mutants had a greater inhibitory effect on cell migration than either mutant alone, indicating that the effects of these mutants were additive rather than suppressive. Finally, these orthogonal promoters were used to dynamically control the motility of multiple cell populations in a three-dimensional matrix, providing a new way to spatially pattern cells. When cells were cultured as multicellular spheroids within a collagen matrix, CA Rac1 expression stimulated cell migration, while DN Rac1 expression strongly inhibited it. Thus the ability to switch these two phenotypes on and off by adding and withdrawing the transcriptional inducers provided a way to control both the timing and the extent of cell migration. To exploit this as a patterning method, cells expressing DN Rac1 from either the doxycycline-inducible promoter or the cumate-inducible promoter were mixed together as multicellular spheroids and then subjected to alternating administration of the two inducers. When the inducer was switched (e.g., doxycycline removed and replaced with cumate), one population was stimulated to migrate while the other was inhibited, and this created radially symmetric patterns of cells over time. The strategies developed in these dissertation studies represent a novel method for tuning cellular mechanical properties and behaviors, which we expect will be useful in a number of tissue engineering applications. In addition, by enabling graded control over the activity of multiple proteins, these methods provide a unique opportunity to investigate the quantitative relationships describing how protein activity levels influence cell behavior. Given that cell and tissue mechanics have been discovered to play critical roles in a number of human diseases, a better understanding of these relationships may lead to new therapeutic targets for disease treatments.
Molecular And Cellular Mechanobiology
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Author : Shu Chien
language : en
Publisher: Springer
Release Date : 2016-08-10
Molecular And Cellular Mechanobiology written by Shu Chien and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016-08-10 with Medical categories.
This book will cover the cutting-edge developments in molecular and cellular mechanobiology to date. Readers will have a clear understanding of mechanobiology at the molecular and cellular levels, encompassing the mechanosensors, transducers, and transcription. An integrative approach across different scales from molecular sensing to mechanotransduction and gene modulation for physiological regulation of cellular functions will be explored, as well as applications to pathophysiological states in disease. A comprehensive understanding of the roles of physicochemical microenvironment and intracellular responses in determining cellular function in health and disease will also be discussed.
Mechanobiology
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Author : Glen L. Niebur
language : en
Publisher: Elsevier
Release Date : 2019-12-01
Mechanobiology written by Glen L. Niebur and has been published by Elsevier this book supported file pdf, txt, epub, kindle and other format this book has been release on 2019-12-01 with Science categories.
Mechanobiology: From Molecular Sensing to Disease will provide a review of the current state of understanding of mechanobiology and its role in health and disease. It covers: Current understanding of the main molecular pathways by which cells sense and respond to mechanical stimuli, A review of diseases that with known or purported mechanobiological underpinnings; The role of mechanobiology in tissue engineering and regenerative medicine; Experimental methods to capture mechanobiological phenomena; Computational models in mechanobiology. Presents our current understanding of the main molecular pathways by which cells sense and respond to mechanical stimuli Provides a review of diseases with known or purported mechanobiological underpinnings Includes the role of mechanobiology in tissue engineering and regenerative medicine Covers experimental methods to capture mechanobiological phenomena
The Cell As A Machine
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Author : Michael Sheetz
language : en
Publisher: Cambridge University Press
Release Date : 2018-01-11
The Cell As A Machine written by Michael Sheetz and has been published by Cambridge University Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018-01-11 with Science categories.
A systematic and mathematically accessible introductory text explaining cell functions through the engineering principles of robust devices.
Forces In Biology Cell And Developmental Mechanobiology And Its Implications In Disease Volume Ii
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Author : Selwin K. Wu
language : en
Publisher: Frontiers Media SA
Release Date : 2023-01-05
Forces In Biology Cell And Developmental Mechanobiology And Its Implications In Disease Volume Ii written by Selwin K. Wu and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2023-01-05 with Science categories.
Physical Principles Of Electro Mechano Biology
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Author : Christian Brosseau
language : en
Publisher: Springer Nature
Release Date : 2023-09-01
Physical Principles Of Electro Mechano Biology written by Christian Brosseau and has been published by Springer Nature this book supported file pdf, txt, epub, kindle and other format this book has been release on 2023-09-01 with Science categories.
This book covers the recently developed understanding of Electro-Mechano-Biology (EMB) in which the focus is primarily on the couplings between the electric and mechanical fields. The emphasis lies on the analytical and computational aspects of EMB at the cellular level. The book is divided into two parts. In the first part, the author starts by defining and discussing the relevant basic aspects of the electrical and mechanical properties of cell membranes. He provides an overview of some of the ways analytical modelling of cell membrane electrodeformation (ED) and electroporation (EP) appears in a variety of contexts as well as a contemporary account of recent developments in computational approaches that can feature in the theory initiative, particularly in its attempt to describe the cohort of activities currently underway. Intended to serve as an introductory text and aiming to facilitate the understanding of the field to non-experts, this part does not dwell on the set of topics, such as cellular mechanosensing and mechanotransduction, irreversible EP, and atomistic molecular dynamics modelling of membrane EP. The second (and larger) part of the book is devoted to a presentation of the necessary analytical and computational tools to illustrate the ideas behind EMB and illuminate physical insights. Brief notes on the history of EMB and its many applications describing the variety of ideas and approaches are also included. In this part, the background of the first principles and practical calculation methods are discussed to highlight aspects that cannot be found in a single volume.
Mechanobiology
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Author : Simon C. F. Rawlinson
language : en
Publisher: John Wiley & Sons
Release Date : 2017-02-06
Mechanobiology written by Simon C. F. Rawlinson and has been published by John Wiley & Sons this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017-02-06 with Science categories.
An emerging field at the interface of biology and engineering, mechanobiology explores the mechanisms by which cells sense and respond to mechanical signals—and holds great promise in one day unravelling the mysteries of cellular and extracellular matrix mechanics to cure a broad range of diseases. Mechanobiology: Exploitation for Medical Benefit presents a comprehensive overview of principles of mechanobiology, highlighting the extent to which biological tissues are exposed to the mechanical environment, demonstrating the importance of the mechanical environment in living systems, and critically reviewing the latest experimental procedures in this emerging field. Featuring contributions from several top experts in the field, chapters begin with an introduction to fundamental mechanobiological principles; and then proceed to explore the relationship of this extensive force in nature to tissues of musculoskeletal systems, heart and lung vasculature, the kidney glomerulus, and cutaneous tissues. Examples of some current experimental models are presented conveying relevant aspects of mechanobiology, highlighting emerging trends and promising avenues of research in the development of innovative therapies. Timely and important, Mechanobiology: Exploitation for Medical Benefit offers illuminating insights into an emerging field that has the potential to revolutionise our comprehension of appropriate cell biology and the future of biomedical research.
Mechanotransduction
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Author :
language : en
Publisher: Academic Press
Release Date : 2014-07-29
Mechanotransduction written by and has been published by Academic Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2014-07-29 with Science categories.
Progress in Molecular Biology and Translational Science provides a forum for discussion of new discoveries, approaches, and ideas in molecular biology. It contains contributions from leaders in their fields and abundant references. Volume 126 features in-depth reviews that focus on the tools required to investigate mechanotransduction. Additional chapters focus on how we can use these tools to answer fundamental questions about the interaction of physical forces with cell biology, morphogenesis, and function of mature structures. Chapters in the volume are authored by a unique combination of cell biologists and engineers, providing a range of perspectives on mechanotransduction. Provides a unique combination of perspectives from biologists and engineers Engaging to people of many training backgrounds
Drosophila Eye Development
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Author : Kevin Moses
language : en
Publisher: Springer Science & Business Media
Release Date : 2002-03-12
Drosophila Eye Development written by Kevin Moses and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2002-03-12 with Medical categories.
1 Kevin Moses It is now 25 years since the study of the development of the compound eye in Drosophila really began with a classic paper (Ready et al. 1976). In 1864, August Weismann published a monograph on the development of Diptera and included some beautiful drawings of the developing imaginal discs (Weismann 1864). One of these is the first description of the third instar eye disc in which Weismann drew a vertical line separating a posterior domain that included a regular pattern of clustered cells from an anterior domain without such a pattern. Weismann suggested that these clusters were the precursors of the adult ommatidia and that the line marks the anterior edge of the eye. In his first suggestion he was absolutely correct - in his second he was wrong. The vertical line shown was not the anterior edge of the eye, but the anterior edge of a moving wave of patterning and cell type specification that 112 years later (1976) Ready, Hansen and Benzer would name the "morphogenetic furrow". While it is too late to hear from August Weismann, it is a particular pleasure to be able to include a chapter in this Volume from the first author of that 1976 paper: Don Ready! These past 25 years have seen an astonishing explosion in the study of the fly eye (see Fig.
Mechanobiology In Health And Disease
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Author : Stefaan Verbruggen
language : en
Publisher: Academic Press
Release Date : 2018-08-09
Mechanobiology In Health And Disease written by Stefaan Verbruggen and has been published by Academic Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018-08-09 with Technology & Engineering categories.
Mechanobiology in Health and Disease brings together contributions from leading biologists, clinicians, physicists and engineers in one convenient volume, providing a unified source of information for researchers in this highly multidisciplinary area. Opening chapters provide essential background information on cell mechanotransduction and essential mechanobiology methods and techniques. Other sections focus on the study of mechanobiology in healthy systems, including bone, tendons, muscles, blood vessels, the heart and the skin, as well as mechanobiology studies of pregnancy. Final chapters address the nascent area of mechanobiology in disease, from the study of bone conditions, skin diseases and heart diseases to cancer. A discussion of future perspectives for research completes each chapter in the volume. This is a timely resource for both early-career and established researchers working on mechanobiology. Provides an essential digest of primary research from many fields and disciplines in one convenient volume Covers both experimental approaches and descriptions of mechanobiology problems from mathematical and numerical perspectives Addresses the hot topic of mechanobiology in disease, a particularly dynamic field of frontier science
