Cardiac Mysin Binding Protein-C Is Essential for Thick-Filament Stability and Flexural Rigidity

• Published in: Biophysical journal Vol. 96; no. 8; p. 3273
• Main Authors: Nyland, Lori R, Palmer, Bradley M, Chen, Zengyi, Maughan, David W, Seidman, Christine E, Seidman, JG, Kreplak, Laurent, Vigoreaux, Jim O
• Format: Journal Article
• Language: English
• Published: New York Biophysical Society 22-04-2009
• Subjects: Binding sites; Cardiovascular system; Microscopy; Proteins; Rodents
• ISSN: 0006-3495; 1542-0086

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 ...m) was significantly (P < 0.01) shorter than +/+ (1.56 ± 0.02 ...m). 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 ...m) compared to +/+ (2.05 ± 0.01 ...m). 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-filamentspecific persistence length in the t/t (373 ± 62 ...m) was significantly lower than in +/+ (639 ± 101 ...m). 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. (ProQuest: ... denotes formulae/symbols omitted.)