Abstract
Using atomic force microscopy, we examined the contribution of cardiac myosin binding protein-C (cMyBP-C) to thick-filament length and flexural rigidity. Native thick filaments were isolated from the hearts of transgenic mice bearing a truncation mutation of cMyBP-C (t/t) that results in no detectable cMyBP-C and from age-matched wild-type controls (+/+). Atomic force microscopy images of these filaments were evaluated with an automated analysis algorithm that identified filament position and shape. The t/t thick-filament length (1.48 ± 0.02 μm) was significantly (P < 0.01) shorter than +/+ (1.56 ± 0.02 μm). This 5%-shorter thick-filament length in the t/t was reflected in 4% significantly shorter sarcomere lengths of relaxed isolated cardiomyocytes of the t/t (1.97 ± 0.01 μm) compared to +/+ (2.05 ± 0.01 μm). To determine if cMyBP-C contributes to the mechanical properties of thick filaments, we used statistical polymer chain mechanics to calculate a per-filament-specific persistence length, an index of flexural rigidity directly proportional to Young's modulus. Thick-filament-specific persistence length in the t/t (373 ± 62 μm) was significantly lower than in +/+ (639 ± 101 μm). Accordingly, Young's modulus of t/t thick filaments was ∼60% of +/+. These results provide what we consider a new understanding for the critical role of cMyBP-C in defining normal cardiac output by sustaining force and muscle stiffness.
Original language | English |
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Pages (from-to) | 3273-3280 |
Number of pages | 8 |
Journal | Biophysical Journal |
Volume | 96 |
Issue number | 8 |
DOIs | |
Publication status | Published - 2009 |
Bibliographical note
Funding Information:This study was funded by National Institutes of Health grant HL59408 (D.W.M. and B.M.P.) and Nationa Science Foundation grants MCB 0315865 and IOB 0718417 (J.O.V.).
ASJC Scopus Subject Areas
- Biophysics