A reaction-subdiffusion model of fluorescence recovery after photobleaching (FRAP)
TL;DR: This work incorporates anomalous diffusion in a previously developed model for FRAP experiments, and finds that this model can be used to obtain excellent fits to experimental data, and derives explicit analytic solutions of the model in certain limits.
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Abstract: Anomalous diffusion, in particular subdiffusion, is frequently invoked as a mechanism of motion in dense biological media, and may have a significant impact on the kinetics of binding/unbinding events at the cellular level. In this work we incorporate anomalous diffusion in a previously developed model for FRAP experiments. Our particular implementation of subdiffusive transport is based on a continuous time random walk (CTRW) description of the motion of fluorescent particles, as CTRWs lend themselves particularly well to the inclusion of binding/unbinding events. In order to model switching between bound and unbound states of fluorescent subdiffusive particles, we derive a fractional reaction-subdiffusion equation of rather general applicability. Using suitable initial and boundary conditions, this equation is then incorporated in the model describing two-dimensional kinetics of FRAP experiments. We find that this model can be used to obtain excellent fits to experimental data. Moreover, recovery curves corresponding to different radii of the circular bleach spot can be fitted by a single set of parameters. While not enough evidence has been collected to claim with certainty that CTRW is the underlying transport mechanism in FRAP experiments, the compatibility of our results with experimental data fuels the discussion as to whether normal diffusion or anomalous diffusion is the appropriate model, and as to whether anomalous diffusion effects are important to fully understand the outcomes of FRAP experiments. On a more technical side, we derive explicit analytic solutions of our model in certain limits.
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Citations
Fractional diffusion equations coupled by reaction terms
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TL;DR: This paper studies the subdiffusion-limited model, which is defined by mesoscopic equations with fractional derivatives applied to both the movement and the reaction terms, and identifies some precise microscopic conditions that dictate when this type of mesoscopic model is or is not appropriate.
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Anomalous reaction-diffusion equations for linear reactions.
TL;DR: Analysis reveals that the evolution equations follow from the probabilistic independence of the stochastic spatial and discrete processes describing a single particle and the linearity of the integro-differential operators describing spatial movement.
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Inferences from FRAP data are model dependent: a subdiffusive analysis.
TL;DR: In this paper , a reaction-subdiffusion model was proposed to interpret FRAP data and shown to be consistent with both diffusive and subdiffusive motion in many scenarios.
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References
Expanding the scope of quantitative FRAP analysis.
Mark A. Hallen,Anita T. Layton +1 more
TL;DR: Numerical results show that using a model that represents the influential physical processes and that is formulated in the appropriate geometry can substantially improve the accuracy of FRAP calculations.
15
Reactions in Subdiffusive Media and Associated Fractional Equations
Santos B. Yuste,Enrique Abad,Katja Lindenberg +2 more
- 01 Oct 2011
TL;DR: In this article, the authors construct and solve fractional equations for the description of reactions in subdiffusive media starting from a mesoscopic continuous time random walk model, and understand the spatial and temporal evolution of the reactant concentrations.
14
Reply to the comment by V. P. Shkilev on "anomalous versus slowed-down Brownian diffusion in the ligand-binding equilibrium".
Hédi Soula,Hédi Soula,Bertrand Caré,Bertrand Caré,Guillaume Beslon,Hugues Berry,Hugues Berry +6 more
TL;DR: Shkilev et al. as discussed by the authors showed that when diffusion is uniformly Brownian with a space-independent diffusion coefficient, the equilibrium fraction of bound receptors should depend on the dif- fusion coefficient and when molecules undergo tran- sient subdiffusion due to a Continuous-Time Random Walk (CTRW).
3
Evidence for a common mode of transcription factor interaction with chromatin as revealed by improved quantitative fluorescence recovery after photobleaching.
TL;DR: The new estimates predict that for each of the three transcription factors, approximately 75% of the molecules are freely diffusing within the nucleus, whereas the remainder is bound with an average residence time of approximately 2.5 s to a single type of chromatin binding site.
Anomalous versus Slowed-Down Brownian Diffusion in the Ligand-Binding Equilibrium
Hédi Soula,Hédi Soula,Bertrand R. Caré,Bertrand R. Caré,Guillaume Beslon,Guillaume Beslon,Hugues Berry,Hugues Berry +7 more
TL;DR: This work compares the (long-time) equilibrium properties obtained with transient anomalous diffusion due to obstacle hindrance or power-law-distributed residence times (continuous-time random walks) to those obtained with space-dependent slowed-down Brownian motion and shows that these three scenarios have distinctive effects on the apparent affinity of the reaction.