Elastic Filaments of the Cell

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.

Preface. Elastic Filaments of the Cell. Connecting Filaments: A Historical Prospective; K. Trombitás. Connectin: From Regular to Giant Sizes of Sarcomeres; K. Maruyama, S. Kimura. Molecular Tools for the Study of Titin's Differential Expression; T. Centner, et al. Sequence and Mechanical Implications of Titin's PEVK Region; M.L. Greaser, et al. Probing the Functional Roles of Titin Ligands in Cardiac Myofibril Assembly and Maintenance; A.S. McElhinny, et al. Assembly of Myofibrils in Cardiac Muscle Cells; J.W. Sanger, et al. General Discussion I. Molecular Mechanism of Elasticity. Mechanical Manipulation of Single Titin Molecules with Laser Tweezers; M.S.Z. Kellermayer, et al. Unfolding Forces of Titin and Fibronectin Domains Directly Measured by AFM; M. Rief, et al. Computer Modeling of Force-Induced Titin Domain Unfolding; H. Lu, et al. Extensibility in the Titin Molecule and its Relation to Muscle Elasticity; L. Tskhovrebova, J. Trinick. Titin Elasticity in the Context of the Sarcomere: Force and Extensibility Measurements on Single Myofibrils; W.A. Linke. Titin-Like Proteins. Links in the Chain: The Contribution of Kettin to the Elasticity of Insect Muscles; B. Bullard, et al. Titin as a Chromosomal Protein; C. Machado, D.J. Andrew. Role of the Elastic Protein Projectin in Stretch Activation and Work Output of Drosophila Flight Muscles; J.O. Vigoreaux, et al. Drosophila Projectin: A Look at Protein Structure and Sarcomeric Assembly; A. Ayme-Southgate, et al. Role of Titin in Nonmuscle and Smooth Muscle Cells; T.C.S. Keller III, et al. Functional Role of Elastic Filaments. Mechanical Properties of Titin Isoforms; H.L. Granzier, et al. Intact Connecting Filaments Change Length in 2.3-nm Quanta; F. Blyakhman, et al. Titin-Thin Filament Interaction and Potential Role in Muscle Function; J.-P. Jin. Is Titin the Length Sensor in Cardiac Muscle? Physiological and Physiopathological Perspectives; J.-Y. Le Guennec, et al. Ca2+-Dependence of Passive Properties of Cardiac Sarcomeres; B.D. Stuyvers, et al. Possible Contribution of Titin Filaments to the Compliant Series Elastic Component in Horseshoe Crab Skeletal Muscle Fibers; H. Sugi, et al. Skeletal Muscle-Specific Calpain, p94, and Connectin/Titin: Their Physiological Functions and Relationship to Limb-Girdle Muscular Dystrophy Type 2A; H. Sorimachi, et al. General Discussion II. From Connecting Filaments to Co-Expression of Titin Isoforms; K. Trombitás, et al. Index.