TY - JOUR
T1 - Computational Tool to Study Perturbations in Muscle Regulation and Its Application to Heart Disease
AU - Barrick, Samantha K.
AU - Clippinger, Sarah R.
AU - Greenberg, Lina
AU - Greenberg, Michael J.
N1 - Publisher Copyright:
© 2019 Biophysical Society
PY - 2019/6/18
Y1 - 2019/6/18
N2 - Striated muscle contraction occurs when myosin thick filaments bind to thin filaments in the sarcomere and generate pulling forces. This process is regulated by calcium, and it can be perturbed by pathological conditions (e.g., myopathies), physiological adaptations (e.g., β-adrenergic stimulation), and pharmacological interventions. Therefore, it is important to have a methodology to robustly determine the impact of these perturbations and statistically evaluate their effects. Here, we present an approach to measure the equilibrium constants that govern muscle activation, estimate uncertainty in these parameters, and statistically test the effects of perturbations. We provide a MATLAB-based computational tool for these analyses, along with easy-to-follow tutorials that make this approach accessible. The hypothesis testing and error estimation approaches described here are broadly applicable, and the provided tools work with other types of data, including cellular measurements. To demonstrate the utility of the approach, we apply it to elucidate the biophysical mechanism of a mutation that causes familial hypertrophic cardiomyopathy. This approach is generally useful for studying muscle diseases and therapeutic interventions that target muscle contraction.
AB - Striated muscle contraction occurs when myosin thick filaments bind to thin filaments in the sarcomere and generate pulling forces. This process is regulated by calcium, and it can be perturbed by pathological conditions (e.g., myopathies), physiological adaptations (e.g., β-adrenergic stimulation), and pharmacological interventions. Therefore, it is important to have a methodology to robustly determine the impact of these perturbations and statistically evaluate their effects. Here, we present an approach to measure the equilibrium constants that govern muscle activation, estimate uncertainty in these parameters, and statistically test the effects of perturbations. We provide a MATLAB-based computational tool for these analyses, along with easy-to-follow tutorials that make this approach accessible. The hypothesis testing and error estimation approaches described here are broadly applicable, and the provided tools work with other types of data, including cellular measurements. To demonstrate the utility of the approach, we apply it to elucidate the biophysical mechanism of a mutation that causes familial hypertrophic cardiomyopathy. This approach is generally useful for studying muscle diseases and therapeutic interventions that target muscle contraction.
UR - http://www.scopus.com/inward/record.url?scp=85065840325&partnerID=8YFLogxK
U2 - 10.1016/j.bpj.2019.05.002
DO - 10.1016/j.bpj.2019.05.002
M3 - Article
C2 - 31126584
AN - SCOPUS:85065840325
SN - 0006-3495
VL - 116
SP - 2246
EP - 2252
JO - Biophysical Journal
JF - Biophysical Journal
IS - 12
ER -