Model of crystallization in a confined space applied to iron uptake and release by ferritin



Many living organisms store iron in solid form, Fe(III), as a crystal in the inner cavity of the ferritin molecule. When iron is needed for biosynthesis, a reducing agent reduces Fe(III) into the soluble form Fe2+ released by ferritin. Crystallization and release processes are reversible, and their rates evolve in an identical way as a function of the number n of iron atoms in the molecule. The rate increases with n, showing a maximum value when n is approximately 1,300, and then stabilizes for the highest values of n, which can reach 4,500. On the other hand, plotting the amount of released iron as a function of time gives curves with a sigmoid shape. The proposed model was based on the theoretical description of different steps involved in crystal growth inside the protein shell: several independent crystals grow freely at the inner protein wall, and then a distribution function takes into account possible overlapping of different crystallite clusters, whose further growth is limited by diminution of the available space inside the cavity. The kinetics derived was then used to calculate the release curve as a function of time. Solving the system of differential mass-balance equations was simplified by describing the ferritin population as a large discrete distribution of species. The model fully fitted and explained the variation in the crystallization rate with n, and the sigmoid shape of the release curve as a function of time obtained experimentally in a thin-layer electrochemical cell.