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Biophysics of Titin in Cardiac Health and Disease

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Biophysics of the Failing Heart

Part of the book series: Biological and Medical Physics, Biomedical Engineering ((BIOMEDICAL))

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Abstract

Titin is a gigantic multifunctional filamentous protein that spans from the Z-disk to the M-band region of the cardiac sarcomere. The elastic I-band region of titin generates passive force during sarcomere stretch that plays important roles in maintaining the structural organization of the sarcomere and that contributes greatly to diastolic stiffness. Recent work has shown that to match hemodynamic demands the mechanical properties of titin can be finely tuned through differential expression of titin isoforms and phosphorylation of titin’s spring-like elements. Titin may also play a role in mechanically sensing sarcomere length changes due to its placement in the sarcomere and extensible, force-bearing I-band region. The precise ways in which titin behaves as a mechanosensor is not well established, but rapid progress is being made in our understanding of the various proteins involved in signaling pathways that interact with titin. Recent work also revealed mutations in the titin gene (TTN) as a major source of familial cardiomyopathies, including mutations in titin’s spring region linked to arrhythmogenic right ventricular dysplasia and mutations in titin’s A-band region responsible for ~30 % of dilated cardiomyopathy (DCM) cases. This chapter discusses the mechanical properties of titin and the role titin plays in cardiac health and disease.

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Acknowledgements

This work was supported by NIH training grant GM084905 and an award from the American Heart Association 11PRE7370083 to B.A., and by NIH HL062881 to H.G.

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Authors and Affiliations

  1. Department of Physics, University of Arizona, Tucson, AZ, 85724, USA

    Brian R. Anderson

  2. Department of Physiology, Molecular Cardiovascular Research Program, Sarver Heart Center, University of Arizona, Tucson, AZ, 85724, USA

    Brian R. Anderson & Henk L. Granzier

  3. MRB 340, 1656 E Mabel St., Tucson, AZ, 85721, USA

    Henk L. Granzier

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Correspondence to Henk L. Granzier .

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Editors and Affiliations

  1. Dept. of Physiology & Biophysics, University of Illinois at Chicago, Chicago, USA

    R. John Solaro

  2. University of Arizona, Tucson, Arizona, USA

    Jil C. Tardiff

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Anderson, B.R., Granzier, H.L. (2013). Biophysics of Titin in Cardiac Health and Disease. In: Solaro, R., Tardiff, J. (eds) Biophysics of the Failing Heart. Biological and Medical Physics, Biomedical Engineering. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7678-8_10

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  • DOI: https://doi.org/10.1007/978-1-4614-7678-8_10

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  • Print ISBN: 978-1-4614-7677-1

  • Online ISBN: 978-1-4614-7678-8

  • eBook Packages: Physics and AstronomyPhysics and Astronomy (R0)

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