Speaker
Description
Actin assembly drives force generation and membrane remodelling (protrusion, budding, tethering). Many actin kinetic models omit explicit energy accounting with force production \cite{Vavylonis2005,Ditlev2009}, limiting reliable coupling to multiscale models of whole-cell remodelling. Prior efforts linking actin kinetics to continuum mechanics often approximate energy flows and omit explicit nucleotide states \cite{Mogilner1996,Gawthrop2025}. Here, we present a modular, thermodynamically consistent actin model combining nucleation, polymerisation, depolymerisation, ATP/ADP states, and force production. Built using a bond graph approach (thermodynamically consistent ODEs) \cite{Gawthrop2025,Gawthrop2014,Rajagopal2022}, the technique preserves energy accounting and provides modular ports for mechanical coupling. The model is currently being used to explore sensitivity and parameter identifiability, with a particular focus on how ATP/ADP state changes influence conservation of thermodynamic consistency, reproduce canonical behaviours (growth regimes, force-velocity relations, nucleotide turnover), and how Gibbs free energies tune relationships. More broadly, this thermodynamically consistent scaffold lays a foundation for predictive multiscale studies of energy consumption during cell migration and protrusion generation.
Bibliography
@article{Vavylonis2005,
author = {Vavylonis, Dimitrios and Yang, Qingbo and O'Shaughnessy, Ben},
title = {Actin Polymerization Kinetics, Cap Structure, and Fluctuations},
journal = {Proceedings of the National Academy of Sciences},
year = {2005},
volume = {102},
pages = {8543--8548},
doi = {10.1073/pnas.0501435102}
}
@article{Ditlev2009,
author = {Ditlev, Jonathon A. and Vacanti, Nathaniel M. and Novak, Igor L. and Loew, Leslie M.},
title = {An Open Model of Actin Dendritic Nucleation},
journal = {Biophysical Journal},
year = {2009},
volume = {96},
pages = {3529--3542},
doi = {10.1016/j.bpj.2009.01.037}
}
@article{Mogilner1996,
author = {Mogilner, A. and Oster, G.},
title = {Cell Motility Driven by Actin Polymerization},
journal = {Biophysical Journal},
year = {1996},
volume = {71},
pages = {3030--3045},
doi = {10.1016/S0006-3495(96)79496-1}
}
@article{Gawthrop2025,
author = {Gawthrop, Peter J. and Pan, Michael and Rajagopal, Vijay},
title = {Energy-Based Modelling of Single Actin Filament Polymerization Using Bond Graphs},
journal = {Journal of The Royal Society Interface},
year = {2025},
volume = {22},
number = {222},
pages = {20240404},
doi = {10.1098/rsif.2024.0404}
}
@article{Gawthrop2014,
author = {Gawthrop, Peter J. and Crampin, Edmund J.},
title = {Energy-Based Analysis of Biochemical Cycles Using Bond Graphs},
journal = {Proceedings of the Royal Society A},
year = {2014},
volume = {470},
pages = {20140459},
doi = {10.1098/rspa.2014.0459}
}
@article{Rajagopal2022,
author = {Rajagopal, Vijay and Arumugam, Senthil and Hunter, Peter J. and Khadangi, Afshin and Chung, Joshua and Pan, Michael},
title = {The Cell Physiome: What Do We Need in a Computational Physiology Framework for Predicting Single-Cell Biology?},
journal = {Annual Review of Biomedical Data Science},
year = {2022},
volume = {5},
pages = {341--366},
doi = {10.1146/annurev-biodatasci-072018-021246}
}
