pH-depended protein shell dis- and reassembly of ferritin nanoparticles revealed by atomic force microscopy

Ferritin, a protein that is present in the human body for a controlled iron storage and release, consists of a ferrihydrite core and a protein shell. Apoferritin, the empty shell of ferritin, can be modified to carry tailored properties exploitable for targeted and direct drug delivery. This protein shell has the ability to dis- and reassemble depending on the pH value of the liquid environment and can thus be filled with the desired substance. Here we observed the dis- and reassembly process of the protein shell of ferritin and apoferritin in situ and in real space using atomic force microscopy. Ferritin and apoferritin nanoparticles adsorbed on a mica substrate exhibited a change in their size by varying the pH value of the surrounding medium. Lowering the pH value of the solution led to a decrease in size of the nanoparticles whereas a successive increase of the pH value increased the particle size again. The pH dependent change in size could be related to the dis- and reassembling of the protein shell of ferritin and apoferritin. Supplementary imaging by bimodal magnetic force microscopy of ferritin molecules accomplished in air revealed a polygonal shape of the core and a three-fold symmetry of the protein shell providing valuable information about the substructure of the nanoparticles.