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 language | English (US) |
|---|---|
| Pages (from-to) | 11549-11558 |
| Number of pages | 10 |
| Journal | Journal of Biological Chemistry |
| Volume | 277 |
| Issue number | 13 |
| DOIs | |
| State | Published - Mar 29 2002 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry
Cite this
Molecular mechanics of cardiac titin's PEVK and N2B spring elements. / Watanabe, Kaori; Nair, Preetha; Labeit, Dietmar; Kellermayer, Mikló S S Z; Greaser, Marion; Labeit, Siegfried; Granzier, Hendrikus "Henk".
In: Journal of Biological Chemistry, Vol. 277, No. 13, 29.03.2002, p. 11549-11558.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Molecular mechanics of cardiac titin's PEVK and N2B spring elements
AU - Watanabe, Kaori
AU - Nair, Preetha
AU - Labeit, Dietmar
AU - Kellermayer, Mikló S S Z
AU - Greaser, Marion
AU - Labeit, Siegfried
AU - Granzier, Hendrikus "Henk"
PY - 2002/3/29
Y1 - 2002/3/29
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0037192845&partnerID=8YFLogxK
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U2 - 10.1074/jbc.M200356200
DO - 10.1074/jbc.M200356200
M3 - Article
C2 - 11799131
AN - SCOPUS:0037192845
VL - 277
SP - 11549
EP - 11558
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 13
ER -