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The nucleated polymerization model is a mathematical framework that has been applied to aggregation and fragmentation processes in both the discrete and continuous settings. In particular, this model has been the canonical framework for analyzing the dynamics of protein aggregates arising in prion and amyloid diseases such as Alzheimer’s and Parkinson’s disease. We present an explicit steady-state solution to the aggregate size distribution governed by the discrete nucleated polymerization equations. Steady-state solutions have been previously obtained under the assumption of continuous aggregate sizes; however, the discrete solution allows for direct computation and parameter inference, as well as facilitates estimates on the accuracy of the continuous approximation. [ABSTRACT FROM AUTHOR]

According to the prion hypothesis, proteins may act in atypical roles as genetic elements of infectivity and inheritance by undergoing self-replicating changes in physical state. While the preponderance of evidence strongly supports this concept particularly in fungi, the detailed mechanisms by which distinct protein forms specify unique phenotypes are emerging concepts. A particularly active area of investigation is the molecular nature of the heritable species, which has been probed through genetic, biochemical, and cell biological experimentation as well as by mathematical modeling. Here, we suggest that these studies are converging to implicate small aggregates composed of prion-state conformers as the transmissible genetic determinants of protein-based phenotypes. [Copyright &y& Elsevier]

Even among cells in the same population, the concentration of a protein or cellular constituent can vary considerably. This heterogeneity can arise from several sources, including differences in kinetic rates between cells and distribution of cellular constituents through cell division. Compartmental models have been used to describe the distribution of the number of divisions undergone by cells in a population. More recently, such models have been coupled with the dynamics of intracellular labels and analytical solutions to the division and label structured population equations have been found. However, such approaches have thus far focused on simple models of intracellular dynamics such as the decay of an intracellular label. In this work, we demonstrate that analytical solutions are possible for more general forms of intracellular dynamics offering the promise to lend mathematical insight into population dynamics in more realistic biological settings. [ABSTRACT FROM AUTHOR]