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Image based validation of dynamical models for cell reorientation
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Lockley, Robert, Ladds, Graham and Bretschneider, Till (2015) Image based validation of dynamical models for cell reorientation. Cytometry Part A, 87 (6). pp. 471-480. doi:10.1002/cyto.a.22600
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Official URL: http://dx.doi.org/10.1002/cyto.a.22600
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. © 2014 The Authors. Published by Wiley Periodicals, Inc.
| Item Type: | Journal Article | ||||||||
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| Subjects: | Q Science > QH Natural history | ||||||||
| Divisions: | Faculty of Science > Centre for Systems Biology Faculty of Medicine > Warwick Medical School |
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| Library of Congress Subject Headings (LCSH): | Cells -- Motility, Dictyostelium, Image analysis, Fluorescence microscopy | ||||||||
| Journal or Publication Title: | Cytometry Part A | ||||||||
| Publisher: | John Wiley & Sons Ltd. | ||||||||
| ISSN: | 1552-4922 | ||||||||
| Official Date: | June 2015 | ||||||||
| Dates: |
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| Volume: | 87 | ||||||||
| Number: | 6 | ||||||||
| Number of Pages: | 10 | ||||||||
| Page Range: | pp. 471-480 | ||||||||
| DOI: | 10.1002/cyto.a.22600 | ||||||||
| Status: | Peer Reviewed | ||||||||
| Publication Status: | Published | ||||||||
| Access rights to Published version: | Open Access | ||||||||
| Funder: | Engineering and Physical Sciences Research Council (EPSRC), Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), Birmingham Science City, Wellcome Trust (London, England), Royal Society (Great Britain) | ||||||||
| Grant number: | BB/G01227X/1 (BBSRC), WT094131MA (WT) | ||||||||
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