Microarchitecture is severely compromised but motor protein function is preserved in dystrophic mdx skeletal muscle.

Friedrich O, Both M, Weber C, Schürmann S, Teichmann MDH, von Wegner F, Fink R, Vogel M, Chamberlain JS, Garbe CS (2010)

Publication Language: English

Publication Status: Published

Publication Type: Journal article, Original article

Publication year: 2010

Journal

Biophysical Journal Biophysical Society

Book Volume: 98

Pages Range: 606-16

Journal Issue: 4

URI: http://www.cell.com/biophysj/abstract/S0006-3495%2809%2901728-7

DOI: 10.1016/j.bpj.2009.11.005

Open Access Link: http://ac.els-cdn.com/S0006349509017287/1-s2.0-S0006349509017287-main.pdf?_tid=2d43a122-7902-11e5-8bd9-00000aacb362&acdnat=1445548776_b4b9baec183a014f5a96e40edb3f056a

Abstract

Progressive force loss in Duchenne muscular dystrophy is characterized by degeneration/regeneration cycles and fibrosis. Disease progression may involve structural remodeling of muscle tissue. An effect on molecular motorprotein function may also be possible. We used second harmonic generation imaging to reveal vastly altered subcellular sarcomere microarchitecture in intact single dystrophic mdx muscle cells (approximately 1 year old). Myofibril tilting, twisting, and local axis deviations explain at least up to 20% of force drop during unsynchronized contractile activation as judged from cosine angle sums of myofibril orientations within mdx fibers. In contrast, in vitro motility assays showed unaltered sliding velocities of single mdx fiber myosin extracts. Closer quantification of the microarchitecture revealed that dystrophic fibers had significantly more Y-shaped sarcomere irregularities ("verniers") than wild-type fibers (approximately 130/1000 microm(3) vs. approximately 36/1000 microm(3)). In transgenic mini-dystrophin-expressing fibers, ultrastructure was restored (approximately 38/1000 microm(3) counts). We suggest that in aged dystrophic toe muscle, progressive force loss is reflected by a vastly deranged micromorphology that prevents a coordinated and aligned contraction. Second harmonic generation imaging may soon be available in routine clinical diagnostics, and in this work we provide valuable imaging tools to track and quantify ultrastructural worsening in Duchenne muscular dystrophy, and to judge the beneficial effects of possible drug or gene therapies.

Authors with CRIS profile

Oliver Friedrich Lehrstuhl für Medizinische Biotechnologie Sebastian Schürmann Lehrstuhl für Medizinische Biotechnologie

Involved external institutions

Ruprecht-Karls-Universität Heidelberg DE Germany (DE) Harvard University US United States (USA) (US) University of Washington US United States (USA) (US) Goethe-Universität Frankfurt am Main DE Germany (DE)

How to cite

APA:

Friedrich, O., Both, M., Weber, C., Schürmann, S., Teichmann, M.D.H., von Wegner, F.,... Garbe, C.S. (2010). Microarchitecture is severely compromised but motor protein function is preserved in dystrophic mdx skeletal muscle. Biophysical Journal, 98(4), 606-16. https://doi.org/10.1016/j.bpj.2009.11.005

MLA:

Friedrich, Oliver, et al. "Microarchitecture is severely compromised but motor protein function is preserved in dystrophic mdx skeletal muscle." Biophysical Journal 98.4 (2010): 606-16.

BibTeX: Download