Bridging the multiscale gap: Identifying cellular parameters from multicellular data

QB Baker, GJ Podgorski, CD Johnson… - … IEEE Conference on …, 2015 - ieeexplore.ieee.org
2015 IEEE Conference on Computational Intelligence in …, 2015ieeexplore.ieee.org
Multiscale models that link sub-cellular, cellular and multicellular components offer powerful
insights in disease development. Such models need a realistic set of parameters to
represent the physical and chemical mechanisms at the sub-cellular and cellular levels to
produce high fidelity multicellular outcomes. However, determining correct values for some
of the parameters is often difficult and expensive using high-throughput microfluidic
approaches. This work presents an alternative approach that estimates cellular parameters …
Multiscale models that link sub-cellular, cellular and multicellular components offer powerful insights in disease development. Such models need a realistic set of parameters to represent the physical and chemical mechanisms at the sub-cellular and cellular levels to produce high fidelity multicellular outcomes. However, determining correct values for some of the parameters is often difficult and expensive using high-throughput microfluidic approaches. This work presents an alternative approach that estimates cellular parameters from spatiotemporal data produced from bioengineered multicellular in vitro experiments. Specifically, we apply a search technique to an integrated cellular and multicellular model of retinal pigment epithelial (RPE) cells to estimate the binding rate and auto-regulation rate of vascular endothelial growth factor (VEGF). Understanding VEGF regulation is critical in treating age-related macular degeneration and many other diseases. The method successfully identifies realistic values for autoregulatory cellular parameters that reproduce the spatiotemporal in vitro experimental data.
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