Cardiac myosin binding protein-C is essential for thick-filament stability and flexural rigidity.
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 microm) was significantly (P < 0.01) shorter than +/+ (1.56 +/- 0.02 microm). 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 microm) compared to +/+ (2.05 +/- 0.01 microm). 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 microm) was significantly lower than in +/+ (639 +/- 101 microm). Accordingly, Young's modulus of t/t thick filaments was approximately 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.
Nyland
Lori R
LR
Department of Biology, University of Vermont, Burlington, Vermont 05405, USA.
Palmer
Bradley M
BM
Chen
Zengyi
Z
Maughan
David W
DW
Seidman
Christine E
CE
Seidman
J G
JG
Kreplak
Laurent
L
Vigoreaux
Jim O
JO
D000465:Algorithms; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D003599:Cytoskeleton / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure*; D055119:Elastic Modulus; D004548:Elasticity; D051379:Mice; D008822:Mice, Transgenic; D018625:Microscopy, Atomic Force; D032383:Myocytes, Cardiac / Q000502:physiology* / Q000648:ultrastructure; D055550:Protein Stability; D012518:Sarcomeres / Q000378:metabolism; D000099163:Myosin Binding Protein C
D002352:Carrier Proteins; D000099163:Myosin Binding Protein C