Experimental and Theoretical Determination of the pH inside the Confinement of a Virus‐Like Particle

Abstract In biology, a variety of highly ordered nanometer‐size protein cages is found. Such structures find increasing application in, for example, vaccination, drug delivery, and catalysis. Understanding the physiochemical properties, particularly inside the confinement of a protein cage, helps to predict the behavior and properties of new materials based on such particles. Here, the relation between the bulk solution pH and the local pH inside a model protein cage, based on virus‐like particles (VLPs) built from the coat proteins of the cowpea chlorotic mottle virus, is investigated. The pH is a crucial parameter in a variety of processes and is potentially significantly influenced by the high concentration of charges residing on the interior of the VLPs. The data show a systematic more acidic pH of 0.5 unit inside the VLP compared to that of the bulk solution for pH values above pH 6, which is explained using a theoretical model based on a Donnan equilibrium. The model agrees with the experimental data over almost two orders of magnitude, while below pH 6 the experimental data point to a buffering capacity of the VLP. These results are a first step in a better understanding of the physiochemical conditions inside a protein cage.