Biophysical modeling and experimental analysis of the dynamics of C. elegans body-wall muscle cells.

This study combines experimental techniques and mathematical modeling to investigate the dynamics of C. elegans body-wall muscle cells. Specifically, by conducting voltage clamp and mutant experiments, we identify key ion channels, particularly the L-type voltage-gated calcium channel (EGL-19) and p...

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Main Authors: Xuexing Du, Jennifer Crodelle, Victor James Barranca, Songting Li, Yunzhu Shi, Shangbang Gao, Douglas Zhou
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-01-01
Series:PLoS Computational Biology
Online Access:https://doi.org/10.1371/journal.pcbi.1012318
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author Xuexing Du
Jennifer Crodelle
Victor James Barranca
Songting Li
Yunzhu Shi
Shangbang Gao
Douglas Zhou
author_facet Xuexing Du
Jennifer Crodelle
Victor James Barranca
Songting Li
Yunzhu Shi
Shangbang Gao
Douglas Zhou
author_sort Xuexing Du
collection DOAJ
description This study combines experimental techniques and mathematical modeling to investigate the dynamics of C. elegans body-wall muscle cells. Specifically, by conducting voltage clamp and mutant experiments, we identify key ion channels, particularly the L-type voltage-gated calcium channel (EGL-19) and potassium channels (SHK-1, SLO-2), which are crucial for generating action potentials. We develop Hodgkin-Huxley-based models for these channels and integrate them to capture the cells' electrical activity. To ensure the model accurately reflects cellular responses under depolarizing currents, we develop a parallel simulation-based inference method for determining the model's free parameters. This method performs rapid parallel sampling across high-dimensional parameter spaces, fitting the model to the responses of muscle cells to specific stimuli and yielding accurate parameter estimates. We validate our model by comparing its predictions against cellular responses to various current stimuli in experiments and show that our approach effectively determines suitable parameters for accurately modeling the dynamics in mutant cases. Additionally, we discover an optimal response frequency in body-wall muscle cells, which corresponds to a burst firing mode rather than regular firing mode. Our work provides the first experimentally constrained and biophysically detailed muscle cell model of C. elegans, and our analytical framework combined with robust and efficient parametric estimation method can be extended to model construction in other species.
format Article
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institution Kabale University
issn 1553-734X
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language English
publishDate 2025-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS Computational Biology
spelling doaj-art-2dfc85d70e384463a840917476bc6aba2025-02-07T05:30:26ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582025-01-01211e101231810.1371/journal.pcbi.1012318Biophysical modeling and experimental analysis of the dynamics of C. elegans body-wall muscle cells.Xuexing DuJennifer CrodelleVictor James BarrancaSongting LiYunzhu ShiShangbang GaoDouglas ZhouThis study combines experimental techniques and mathematical modeling to investigate the dynamics of C. elegans body-wall muscle cells. Specifically, by conducting voltage clamp and mutant experiments, we identify key ion channels, particularly the L-type voltage-gated calcium channel (EGL-19) and potassium channels (SHK-1, SLO-2), which are crucial for generating action potentials. We develop Hodgkin-Huxley-based models for these channels and integrate them to capture the cells' electrical activity. To ensure the model accurately reflects cellular responses under depolarizing currents, we develop a parallel simulation-based inference method for determining the model's free parameters. This method performs rapid parallel sampling across high-dimensional parameter spaces, fitting the model to the responses of muscle cells to specific stimuli and yielding accurate parameter estimates. We validate our model by comparing its predictions against cellular responses to various current stimuli in experiments and show that our approach effectively determines suitable parameters for accurately modeling the dynamics in mutant cases. Additionally, we discover an optimal response frequency in body-wall muscle cells, which corresponds to a burst firing mode rather than regular firing mode. Our work provides the first experimentally constrained and biophysically detailed muscle cell model of C. elegans, and our analytical framework combined with robust and efficient parametric estimation method can be extended to model construction in other species.https://doi.org/10.1371/journal.pcbi.1012318
spellingShingle Xuexing Du
Jennifer Crodelle
Victor James Barranca
Songting Li
Yunzhu Shi
Shangbang Gao
Douglas Zhou
Biophysical modeling and experimental analysis of the dynamics of C. elegans body-wall muscle cells.
PLoS Computational Biology
title Biophysical modeling and experimental analysis of the dynamics of C. elegans body-wall muscle cells.
title_full Biophysical modeling and experimental analysis of the dynamics of C. elegans body-wall muscle cells.
title_fullStr Biophysical modeling and experimental analysis of the dynamics of C. elegans body-wall muscle cells.
title_full_unstemmed Biophysical modeling and experimental analysis of the dynamics of C. elegans body-wall muscle cells.
title_short Biophysical modeling and experimental analysis of the dynamics of C. elegans body-wall muscle cells.
title_sort biophysical modeling and experimental analysis of the dynamics of c elegans body wall muscle cells
url https://doi.org/10.1371/journal.pcbi.1012318
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