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Abstract Jeroen Cornelissen

Chemistry in the Confinement of Protein Cages

It is recently recognized that protein cages are common structures in biology that can have profoundly different functional properties [1]. The majority of these icosahedral organized particles is found in viruses, structures designed to hijack the molecular machinery of the host cell, while in a variety of bacteria these protein cages have organelle-like functions. In our group we have employed the protein cage of the Cowpea Chlorotic Mottle Virus (CCMV) as a nanoreactor and scaffold for functional materials [2]. The novel properties introduced to this biological nanostructure combined with the enormous variety of existing protein cages with more complex and/or sophisticated architecture has led to the firm believe that new materials with interesting, chemical, physical and biological, properties are accessible.

In the awarded ERC project, I aim to study chemical processes in nano-sized protein cages as mimics of bacterial organelles and to increase the general understanding of chemistry in confinement. Towards this goal we will investigate the controlled in vivo loading of bacterial protein cages, i.e. encapsulins, with proteins and enzymes. This will allow us to study in detail the chemical conversions that take place inside such capsules and it will increase understanding about the reasons why certain processes inside these simple organisms are encased in the protein organelles.

Completely artificial protein organelles will be constructed by in vitro processes using the well-studied Cowpea Chlorotic Mottle virus cage. By employing DNA technology, cages will be loaded with a single enzyme, a sequence of enzymes or molecular probes. By obtaining this high level of control, we can not only study chemical conversions on the inside, but it will also allow us to monitor the physiochemical properties, such as internal pH, polarity and porosity of the protein mantle by encasing the relevant probes or host/guest systems.

In the ultimate stage of the proposed project the formed artificial organelles will be brought into cells in order to interact with the cell metabolism. CCMV has to be introduced by surface modification, while encapsulins can be formed inside these cells; albeit with different cargo. Such experiments have, to my knowledge, not been carried out and introducing new reactions inside these organisms can lead to new potentially interesting products or interfere with cell vitality. The latter can be of importance for the controlled disruption of bacterial cells.

1. S. Kang, T. Douglas Science (2010) 327, 42.

2. A. de la Escosura, R.J.M. Nolte. J.J.L.M. Cornelissen J. Mat. Chem. (2009) 16, 2274.