Molecular mechanics of cardiac titin's PEVK and N2B spring elements

Kaori Watanabe, Preetha Nair, Dietmar Labeit, Mikló S S Z Kellermayer, Marion Greaser, Siegfried Labeit, Hendrikus "Henk" Granzier

Research output: Contribution to journalArticle

104 Scopus citations

Abstract

Titin is a giant elastic protein that is responsible for the majority of passive force generated by the myocardium. Titin's force is derived from its extensible I-band region, which, in the cardiac isoform, comprises three main extensible elements: tandem Ig segments, the PEVK domain, and the N2B unique sequence (N2B-Us). Using atomic force microscopy, we characterized the single molecule force-extension curves of the PEVK and N2B-Us spring elements, which together are responsible for physiological levels of passive force in moderately to highly stretched myocardium. Stretch-release force-extension curves of both the PEVK domain and N2B-Us displayed little hysteresis: the stretch and release data nearly overlapped. The force-extension curves closely followed worm-like chain behavior. Histograms of persistence length (measure of chain bending rigidity) indicated that the single molecule persistence lengths are ∼1.4 and ∼0.65 nm for the PEVK domain and N2B-Us, respectively. Using these mechanical characteristics and those determined earlier for the tandem Ig segment (assuming folded Ig domains), we modeled the cardiac titin extensible region in the sarcomere and calculated the extension of the various spring elements and the forces generated by titin, both as a function of sarcomere length. In the physiological sarcomere length range, predicted values and those obtained experimentally were indistinguishable.

Original languageEnglish (US)
Pages (from-to)11549-11558
Number of pages10
JournalJournal of Biological Chemistry
Volume277
Issue number13
DOIs
Publication statusPublished - Mar 29 2002
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry

Cite this

Watanabe, K., Nair, P., Labeit, D., Kellermayer, M. S. S. Z., Greaser, M., Labeit, S., & Granzier, H. H. (2002). Molecular mechanics of cardiac titin's PEVK and N2B spring elements. Journal of Biological Chemistry, 277(13), 11549-11558. https://doi.org/10.1074/jbc.M200356200