Design of Protein Cage –Based Biohybrid Materials

Joona Mikkilä

Research output: ThesisDoctoral ThesisCollection of Articles


Nature-mimicking bottom-up approaches, such as molecular self-assembly and biotemplating, enable the preparation of highly organized objects with nanometer-scale precision. In addition, the utilization of biomacromolecules as building blocks or structure-directing agents in nanomaterials can lead to the development of highly biocompatible functional systems that can be prepared in mild and environmentally friendly conditions. This thesis demonstrates how functional and self-assembling biohybrid materials can be prepared by combining viruses and protein cages together with synthetic molecules, proteins and DNA origamis. In publication I amphiphilic Janus-dendrimers were synthesized and electrostatically co-assembled together with native Cowpea chlorotic mottle virus (CCMV) particles to study how the structure of different dendrimers affects the assembly process. The resulting complexes resembled naturally occurring inclusion bodies and could therefore benefit their research as a model system.In publication II a water-soluble phthalocyanine was combined with 1,3,6,8-pyrenetetrasulfonic acid and apoferritin protein cages to obtain photoactive crystals. The structure and size of the self-assembling crystals could be adjusted by changing the electrolyte concentration. Most importantly, the crystals were able to generate highly reactive singlet oxygen under irradiation of visible light and could therefore be utilized as an oxidizing agent.In publication III crystalline superlattices were prepared by combining different biomacromolecules. CCMV particles and avidin proteins were self-assembled into binary crystals that could be pre- or post-functionalized through interaction between avidin and different biotin-tagged functional groups such as enzymes, plasmonic gold nanoparticles and fluorescent dyes.In publication IV the tendency of CCMV capsid proteins (CP) to bind onto genetic material was utilized to coat DNA origami structures to obtain enhanced delivery of the origamis inside cells. Due to the fully programmable and therefore easily functionalized nature of DNA origamis, the presented method could be applied, for example, in the delivery of DNA origami conjugated compounds. Taken together, these studies show how multivalency, hydrophobicity, electrolyte concentration as well as particle size and shape affect the structure of self-assembling complexes and crystals. This information can be further applied when designing and creating new functional biohybrid materials.
Translated title of the contributionProteiinihäkkeihin perustuvat biohybridimateriaalit
Original languageEnglish
QualificationDoctor's degree
Awarding Institution
  • Aalto University
  • Kostiainen, Mauri, Supervising Professor
  • Kostiainen, Mauri, Thesis Advisor
Print ISBNs978-952-60-6788-9
Electronic ISBNs978-952-60-6789-6
Publication statusPublished - 2016
MoE publication typeG5 Doctoral dissertation (article)


  • biohybrid material
  • protein cage
  • self-assembly
  • virus
  • dendron
  • dendrimer
  • DNA origami

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