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Open AccessArticle

Estimation of Forces on Actin Filaments in Living Muscle from X-ray Diffraction Patterns and Mechanical Data

1
Department of Biological Sciences, Illinois Institute of Technology, Chicago, IL 60616, USA
2
Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA
3
Bioengineering Research and Development Center (BioIRC), 34000 Kragujevac, Serbia
4
Faculty of Engineering, University of Kragujevac, 34000 Kragujevac, Serbia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(23), 6044; https://doi.org/10.3390/ijms20236044
Received: 25 August 2019 / Revised: 12 November 2019 / Accepted: 26 November 2019 / Published: 30 November 2019
(This article belongs to the Special Issue Sarcomeric Proteins in Health and Disease)
Many biological processes are triggered or driven by mechanical forces in the cytoskeletal network, but these transducing forces have rarely been assessed. Striated muscle, with its well-organized structure provides an opportunity to assess intracellular forces using small-angle X-ray fiber diffraction. We present a new methodology using Monte Carlo simulations of muscle contraction in an explicit 3D sarcomere lattice to predict the fiber deformations and length changes along thin filaments during contraction. Comparison of predicted diffraction patterns to experimental meridional X-ray reflection profiles allows assessment of the stepwise changes in intermonomer spacings and forces in the myofilaments within living muscle cells. These changes along the filament length reflect the effect of forces from randomly attached crossbridges. This approach enables correlation of the molecular events, such as the current number of attached crossbridges and the distributions of crossbridge forces to macroscopic measurements of force and length changes during muscle contraction. In addition, assessments of fluctuations in local forces in the myofilaments may reveal how variations in the filament forces acting on signaling proteins in the sarcomere M-bands and Z-discs modulate gene expression, protein synthesis and degradation, and as well to mechanisms of adaptation of muscle in response to changes in mechanical loading. View Full-Text
Keywords: multiscale model; X-ray fiber diffraction; forces in myofilaments; MUSICO; mechanotransduction multiscale model; X-ray fiber diffraction; forces in myofilaments; MUSICO; mechanotransduction
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Mijailovich, S.M.; Prodanovic, M.; Irving, T.C. Estimation of Forces on Actin Filaments in Living Muscle from X-ray Diffraction Patterns and Mechanical Data. Int. J. Mol. Sci. 2019, 20, 6044.

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