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Sci Rep. 2018 Mar 14;8(1):4559. doi: 10.1038/s41598-018-22506-3.

Computational Methods for Estimating Molecular System from Membrane Potential Recordings in Nerve Growth Cone.

Author information

1
Graduate School of Information Science, Nara Institute of Science and Technology, Nara, Japan.
2
Department of Biochemistry, New York University School of Medicine, New York, USA.
3
Graduate School of Informatics, Kyoto University, Kyoto, Japan.
4
Graduate School of Biological Sciences, Nara Institute of Science and Technology, Nara, Japan.
5
Department of Biochemistry, New York University School of Medicine, New York, USA. kyonsoo.hong@kasahtechnology.com.
6
KASAH Technology, Inc, New York, USA. kyonsoo.hong@kasahtechnology.com.
7
Graduate School of Biological Sciences, Nara Institute of Science and Technology, Nara, Japan. saku@bs.naist.jp.
8
School of Information Science and Technology, Aichi Prefectural University, Aichi, Japan. saku@bs.naist.jp.

Abstract

Biological cells express intracellular biomolecular information to the extracellular environment as various physical responses. We show a novel computational approach to estimate intracellular biomolecular pathways from growth cone electrophysiological responses. Previously, it was shown that cGMP signaling regulates membrane potential (MP) shifts that control the growth cone turning direction during neuronal development. We present here an integrated deterministic mathematical model and Bayesian reversed-engineering framework that enables estimation of the molecular signaling pathway from electrical recordings and considers both the system uncertainty and cell-to-cell variability. Our computational method selects the most plausible molecular pathway from multiple candidates while satisfying model simplicity and considering all possible parameter ranges. The model quantitatively reproduces MP shifts depending on cGMP levels and MP variability potential in different experimental conditions. Lastly, our model predicts that chloride channel inhibition by cGMP-dependent protein kinase (PKG) is essential in the core system for regulation of the MP shifts.

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