Inferences from FRAP data are model dependent: A subdiffusive analysis

基于 FRAP 数据的推断取决于模型:亚扩散分析

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Abstract

Fluorescence recovery after photobleaching (FRAP) is a widely used biological experiment to study the kinetics of molecules that react and move randomly. Since the development of FRAP in the 1970s, many reaction-diffusion models have been used to interpret FRAP data. However, intracellular molecules are widely observed to move by anomalous subdiffusion instead of normal diffusion. In this article, we extend a popular reaction-diffusion model of FRAP to the case of subdiffusion modeled by a fractional diffusion equation. By analyzing this reaction-subdiffusion model, we show that FRAP data are consistent with both diffusive and subdiffusive motion in many scenarios. We illustrate this general result by fitting our model to FRAP data from glucocorticoid receptors in a cell nucleus. We further show that the assumed model of molecular motion (normal diffusion or subdiffusion) strongly impacts the biological parameter values inferred from a given experimentally observed FRAP curve. We additionally analyze our model in three simplified parameter regimes and discuss parameter identifiability for varying subdiffusion exponents.

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