Elastic Filaments of the Cell

Overview

Elastic filaments refer mainly to titin, the largest of all known proteins. Titin was discovered initially in muscle cells, where it interconnects the thick filament with the Z-line. Titin forms a molecular spring that is responsible for maintaining the structural integrity of contracting muscle, ensuring efficient muscle contraction. More recently, it has become clear that titin is not restricted to muscle cells alone. For example, titin is found in chromosomes of neurons and also in blood platelets. This topic ...

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Overview

Elastic filaments refer mainly to titin, the largest of all known proteins. Titin was discovered initially in muscle cells, where it interconnects the thick filament with the Z-line. Titin forms a molecular spring that is responsible for maintaining the structural integrity of contracting muscle, ensuring efficient muscle contraction. More recently, it has become clear that titin is not restricted to muscle cells alone. For example, titin is found in chromosomes of neurons and also in blood platelets. This topic is fast becoming a focal point for research in understanding viscoelastic properties at the molecular, cellular, and tissue levels. In titin may lie a generic basis for biological viscoelasticity. It has become clear that titin may hold the key to certain clinical anomalies. For example, it is clear that titin-based ventricular stiffness is modulated by calcium and that titin is responsible for the altered stiffness in cardiomyopathies. It is also clear from evidence from a group of Finnish families that titin mutations may underlie some muscular dystrophies and that with other mutations chromatids fail to separate during mitosis. Thus, it is clear that this protein will have important clinical implications stemming from its biomechanical role. One aspect of this field is the bringing together of bioengineers with clinical researchers and biologists. Genetic and biochemical aspects of titin-related proteins are being studied together with front-line engineering approaches designed to measure the mechanics of titin either in small aggregates or in single molecules.

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Editorial Reviews

Booknews
Contains proceedings of a June 1999 conference held at the University of Washington, focusing on progress made in understanding elastic protein filaments. Papers are in sections on elastic filaments of the cell, molecular mechanism of elasticity, titin-like proteins, and the functional role of elastic filaments. Specific topics include computer modeling of force-induced titin domain unfolding, the contribution of kettin to the elasticity of insect muscles, mechanical properties of titin isoforms, and titin-thin filament interaction and potential role in muscle function. Granzier is affiliated with Washington State University; Pollack with the University of Washington. Annotation c. Book News, Inc., Portland, OR (booknews.com)
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Product Details

Table of Contents

Elastic Filaments of the Cell
Connecting Filaments: A Historical Prospective 1
Connectin: From Regular to Giant Sizes of Sarcomeres 25
Molecular Tools for the Study of Titin's Differential Expression 35
Sequence and Mechanical Implications of Titin's PEVK Region 53
Probing the Functional Roles of Titin Ligands in Cardiac Myofibril Assembly and Maintenance 67
Assembly of Myofibrils in Cardiac Muscle Cells 89
General Discussion I 107
Molecular Mechanism of Elasticity
Mechanical Manipulation of Single Titin Molecules with Laser Tweezers 111
Unfolding Forces of Titin and Fibronectin Domains Directly Measured by AFM 129
Computer Modeling of Force-Induced Titin Domain Unfolding 143
Extensibility in the Titin Molecule and Its Relation to Muscle Elasticity 163
Titin Elasticity in the Context of the Sarcomere: Force and Extensibility Measurements on Single Myofibrils 179
Titin-Like Proteins
Links in the Chain: The Contribution of Kettin to the Elasticity of Insect Muscles 207
Titin as a Chromosomal Protein 221
Role of the Elastic Protein Projectin in Stretch Activation and Work Output of Drosophila Flight Muscles 237
Drosophila Projectin: A Look at Protein Structure and Sarcomeric Assembly 251
Role of Titin in Nonmuscle and Smooth Muscle Cells 265
Functional Role of Elastic Filaments
Mechanical Properties of Titin Isoforms 283
Intact Connecting Filaments Change Length in 2.3-nm Quanta 305
Titin-Thin Filament Interaction and Potential Role in Muscle Function 319
Is Titin the Length Sensor in Cardiac Muscle? Physiological and Physiopathological Perspectives 337
Ca[superscript 2+]-Dependence of Passive Properties of Cardiac Sarcomeres 353
Possible Contribution of Titin Filaments to the Compliant Series Elastic Component in Horseshoe Crab Skeletal Muscle Fibers 371
Skeletal Muscle-Specific Calpain, p94, and Connectin/Titin: Their Physiological Functions and Relationship to Limb-Girdle Muscular Dystrophy Type 2A 383
General Discussion II 399
From Connecting Filaments to Co-Expression of Titin Isoforms 405
Index 419
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