Compartment models have been used to describe the time evolution of a system undergoing reactions between populations in different compartments. The governing equations are a set of coupled ordinary differential equations. In recent years fractional order derivatives have been introduced in compartment models in an ad hoc way, replacing ordinary derivatives with fractional derivatives. This has been motivated by the utility of fractional derivatives in incorporating history effects, but the ad hoc inclusion can be problematic for flux balance. To overcome these problems we have derived fractional order compartment models from an underlying physical stochastic process. In general, our fractional compartment models differ from ad hoc fractional models and our derivation ensures that the fractional derivatives have a physical basis in our models. Some illustrative examples, drawn from epidemiology, pharmacokinetics, and in-host virus dynamics, are provided.

Particle-tracking experiments focusing on virions or nanoparticles in mucus have measured mean-square displacements and reported diffusion coefficients that are orders of magnitude smaller than the diffusion coefficients of such particles in water. Accurate description of this subdiffusion is important to properly estimate the likelihood of virions traversing the mucus boundary layer and infecting cells in the epithelium. However, there are several candidate models for diffusion that can fit experimental measurements of mean-square displacements. We show that these models yield very different estimates for the time taken for subdiffusive virions to traverse through a mucus layer. We explain why fits of subdiffusive mean-square displacements to standard diffusion models may be misleading. Relevant to human immunodeficiency virus infection, using computational methods for fractional subdiffusion, we show that subdiffusion in normal acidic mucus provides a more effective barrier against infection than previously thought. By contrast, the neutralization of the mucus by alkaline semen, after sexual intercourse, allows virions to cross the mucus layer and reach the epithelium in a short timeframe. The computed barrier protection from fractional subdiffusion is some orders of magnitude greater than that derived by fitting standard models of diffusion to subdiffusive data.

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