title: Image based validation of dynamical models for cell reorientation.
abstract: A key feature of directed cell movement is the ability of cells to reorient quickly in response to changes in the direction of an extracellular stimulus. Mathematical models have suggested quite different regulatory mechanisms to explain reorientation, raising the question of how we can validate these models in a rigorous way. In this study, we fit three reaction-diffusion models to experimental data of Dictyostelium amoebae reorienting in response to alternating gradients of mechanical shear flow. The experimental readouts we use to fit are spatio-temporal distributions of a fluorescent reporter for cortical F-actin labeling the cell front. Experiments performed under different conditions are fitted simultaneously to challenge the models with different types of cellular dynamics. Although the model proposed by Otsuji is unable to provide a satisfactory fit, those suggested by Meinhardt and Levchenko fit equally well. Further, we show that reduction of the three-variable Meinhardt model to a two-variable model also provides an excellent fit, but has the advantage of all parameters being uniquely identifiable. Our work demonstrates that model selection and identifiability analysis, commonly applied to temporal dynamics problems in systems biology, can be a powerful tool when extended to spatio-temporal imaging data.
authors.affiliation: Warwick Systems Biology Centre, Senate House, University of Warwick, Coventry, CV4 7AL, United Kingdom.
authors.forename: Robert
authors.initials: R
authors.lastname: Lockley
authors.affiliation: Division of Biomedical Cell Biology, Warwick Medical School, University of Warwick, Coventry, CV4 7AL, United Kingdom.
authors.forename: Graham
authors.initials: G
authors.lastname: Ladds
authors.affiliation: Warwick Systems Biology Centre, Senate House, University of Warwick, Coventry, CV4 7AL, United Kingdom.
authors.forename: Till
authors.initials: T
authors.lastname: Bretschneider
mesh_terms: D000199:Actins / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D019295:Computational Biology / Q000379:methods; D004023:Dictyostelium / Q000502:physiology*; D057446:Hydrodynamics; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D008962:Models, Theoretical; D049490:Systems Biology / Q000379:methods
chemical_list: D000199:Actins
keywords: Dictyostelium; actin; cell reorientation; fluorescence microscopy; identifiability analysis; image based model fitting; spatio-temporal pattern formation