TY - JOUR
T1 - Tropomyosin dynamics during cardiac muscle contraction as governed by a multi-well energy landscape
AU - Aboelkassem, Yasser
AU - Trayanova, Natalia
N1 - Funding Information:
The authors acknowledge Dr. Anthony Cammarato, Johns Hopkins University for his insightful discussions and Dr. Andrew D. McCulloch, University of California San Diego for his expert feedback on the final draft of this study. The authors gratefully acknowledge funding from the Leducq Foundation Network of Excellence grant Repolarization HeterogeneitY imaging for personalized Therapy of Heart arrhythmia. This work was supported in part by the National Institutes of Health awards DP1 HL123271 and R01HL103428.
Funding Information:
The authors gratefully acknowledge funding from the Leducq Foundation Network of Excellence grant Repolarization HeterogeneitY imaging for personalized Therapy of Heart arrhythmia. This work was supported in part by the National Institutes of Health awards DP1 HL123271 and R01HL103428 .
Publisher Copyright:
© 2018 Elsevier Ltd
PY - 2019/7
Y1 - 2019/7
N2 - The dynamic oscillations of tropomyosin molecules in the azimuthal direction over the surface of the actin filament during thin filament activation are studied here from an energy landscape perspective. A mathematical model based on principles from nonlinear dynamics and chaos theory is derived to describe these dynamical motions. In particular, an energy potential with three wells is proposed to govern the tropomyosin oscillations between the observed regulatory positions observed during muscle contraction, namely the blocked “B”, closed “C” and open “M” states. Based on the variations in both the frequency and amplitude of the environmental (surrounding the thin filament system) driving tractions, such as the electrostatic, hydrophobic, and Ca2+-dependent forces, the tropomyosin movements are shown to be complex; they can change from being simple harmonic oscillations to being fully chaotic. Three cases (periodic, period-2, and chaotic patterns) are presented to showcase the different possible dynamic responses of tropomyosin sliding over the actin filament. A probability density function is used as a statistical measure to calculate the average residence time spanned out by the tropomyosin molecule when visiting each (B, C, M) equilibrium state. The results were found to depend strongly on the energy landscape profile and its featured barriers, which normally govern the transitions between the B-C-M states during striated muscle activation.
AB - The dynamic oscillations of tropomyosin molecules in the azimuthal direction over the surface of the actin filament during thin filament activation are studied here from an energy landscape perspective. A mathematical model based on principles from nonlinear dynamics and chaos theory is derived to describe these dynamical motions. In particular, an energy potential with three wells is proposed to govern the tropomyosin oscillations between the observed regulatory positions observed during muscle contraction, namely the blocked “B”, closed “C” and open “M” states. Based on the variations in both the frequency and amplitude of the environmental (surrounding the thin filament system) driving tractions, such as the electrostatic, hydrophobic, and Ca2+-dependent forces, the tropomyosin movements are shown to be complex; they can change from being simple harmonic oscillations to being fully chaotic. Three cases (periodic, period-2, and chaotic patterns) are presented to showcase the different possible dynamic responses of tropomyosin sliding over the actin filament. A probability density function is used as a statistical measure to calculate the average residence time spanned out by the tropomyosin molecule when visiting each (B, C, M) equilibrium state. The results were found to depend strongly on the energy landscape profile and its featured barriers, which normally govern the transitions between the B-C-M states during striated muscle activation.
KW - Cardiac muscle contraction
KW - Chaos theory
KW - Myofilament modeling
KW - Tropomyosin dynamics
UR - https://www.scopus.com/pages/publications/85052159134
UR - https://www.scopus.com/pages/publications/85052159134#tab=citedBy
U2 - 10.1016/j.pbiomolbio.2018.07.015
DO - 10.1016/j.pbiomolbio.2018.07.015
M3 - Article
C2 - 30145015
AN - SCOPUS:85052159134
SN - 0079-6107
VL - 144
SP - 102
EP - 115
JO - Progress in Biophysics and Molecular Biology
JF - Progress in Biophysics and Molecular Biology
ER -