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Martijn Verwegen

Protein cage clustering

Towards functional biohybrid materials

Promotion date: September 6.

Promotor: Prof. dr. Jeroen Cornelissen

Virus based protein cages offer immense chemical and structural flexibility whilst retaining a monodisperse and symmetrically organized structure that is unrivalled by any artificial nanoparticle. This allows them alongside with virus-like particles (VLPs), created by modifying an existing protein cage, to be used as programmable nano building blocks for the formation of complex nano structures.

It is investigated how control over the loading and assembly of protein cages, can result in functional materials. The Cowpea Chlorotic Mottle Virus (CCMV) is used as a basis. Model VLPs were formed by encapsulation of gold particles. The presented method can be extended to efficiently encapsulate other anionic nanoparticles.

Better understanding the differences in clustering CCMV based VLPs, a further step is made towards functional materials. With a variety of cores and clustering materials, available VLP based clustering is not limited to using soft macromolecules. Particularly, hard nanoparticles offer a wide range of interesting physical properties that could lead to new material properties.

The clustering of VLPs seems promising. Clusters of VLPs are shown to be fast and easy to make compared to traditional protein crystallization techniques. Such clustering is dependent on the structure, the size and resulting symmetry of the VLPs.

Furthermore, this thesis shows proof that these clusters allow us to alter the physical properties of their environment, based on the core composition. This would allow for a wide variety of systems to be designed, from mixed hard nanoparticle systems to carefully constructed multiple enzymatic pathways inside the same material.

What were the first stages of your PhD project work?

The ultimate goal was to construct functional virus based materials in order to locally influence some physical property, in this case that of light. This required a succession of intermediate stages, the first of which was to fabricate the building blocks by breaking open the protein cages and replacing the genetic material inside. This was the basic first step towards creating new functional building blocks.

After coupling fluorophores to the gold containing protein cages, we noticed fluorescence enhancement after which we were able to show these properties were preserved after clustering. In fact, the first experiment showed very good results right away. This positive result I experienced intensely, as I had worked towards this crucial experiment for two years at that time.

Your work is fundamental in nature. How can we think of future applications?

All in all, the results of this work strengthen the belief that more varieties in building blocks are feasible and more functionalities could be added in later stages. The modular functionality and ability to form clusters, make VLPs suitable for future applications, for example in designing alternative ways to master photonic circuitry.

One of my theses is that: any system based on virus-like particles will suffer from biological complexity in trying to study and control them. In my opinion this is not a major setback, as nature offers by far the best prospects to succeed in controlling the organization of material, using strategies already proven in the course of evolutionary selection, and to which we can add new functionality.

Furthermore VLP structures could be promising for mimicking properties in cellular environments one day.

Can you mention some journals you published in?

An article appeared in Chemical Communications. At the moment two further manuscripts are in preparation and two more have been submitted, of which one is accepted now already.

In what way did you develop personally, as a researcher and scientist, during your PhD period?

I learned to systematically study the variables and parameters as well as their contribution to the phenomena and processes. It is required sometimes to study one isolated issue thoroughly, for example by working on one single graph for some weeks in a row, in order to characterize one particular experiment. Working patiently and steadily is important to achieve scientific results that matter.

Apart from this, I am convinced of the importance of broadening one’s view, not focusing on scientific research too heavily. For example, I benefitted from training my theatre skills, improvising during performances as an actor. Embedding creativity within active relaxing activities, led to positive energy also useful for my scientific work. Sometimes I was able to come up with new ideas and strategies for further research the day after or the very same evening. Apart from theatre, I am sure that singing and board games, or other forms of cultural activities, may have similar results.

What are your future plans?

At the moment I am working as a policy officer at NWO. This Dutch organization is the main financer of scientific research in the Netherlands. As an advisor working for the board, I now focus on three subjects: one on valorization of knowledge for industry and for society, and one on the Dutch policy towards the national research institutes active in The Netherlands, such as FOM and Astron.

The third project is very special indeed. It concerns coordinating a European project within a large-scale international “Big Science” project on astronomy: the Square Kilometer Array. Here coupled telescopes send their data which are analyzed altogether. It is a great feeling to be involved in a gigantic project like this. It reflects my passion for science and my generalist attitude.

What, in your opinion, is important for Mesa+ to stay successful in future?

The facilities and equipment available at Mesa+ are of world class standard. I find it important for Mesa+ to position itself as a sound national institution, like they already do by contributing prominently to the NanoNext programs. Also I believe Mesa+ can contribute to the region of Twente even more as they already do, for example by developing new up-to-date equipment in collaboration with industrial companies situated in the region. This spin-out approach will enhance the knowledge base and competitiveness of these regional enterprises. Such technological transfer activities will offer new chances to excel on an international stage. This will induce an ongoing contribution to the regional and national economy.