Nanoparticle-protein interactions: Technique development and interaction studies

Research output: Book/anthology/dissertation/reportPh.D. thesisResearch

  • Christina Moeslund Zeuthen
Nanoparticles are an important modern material used in both drug delivery and many commercial products, where they may come into contact with patients, workers and members of the public. Upon entering the body, the nanoparticles interact with proteins, which form a dynamic protein corona that determines the biological destination of the particles. Some proteins in the corona, such as the complement protein C1q, help clear the nanoparticles from the body using the immune system. The role of the elusive soft protein corona has been a topic of discussion for many years, due to a lack of methods to investigate it, which leads to a lack of data.
The overall aim of this PhD thesis has been to progress the field of protein-nanoparticle interactions. The first project was to develop an analytical method for measuring protein-nanoparticle interactions in solution, which would allow better investigation of the soft protein corona. The search led to the discovery that many different nanoparticles can adsorb onto surfaces functionalised with protein-rejecting polymer, which creates a sensor surface that allows measurement of nanoparticle-protein interactions. The forces behind the nanoparticle-polymer interactions were investigated, and it was concluded that a mixture of electrostatic forces, hydrophobic and Van der Waals interactions led to the adsorption of the nanoparticles. This novel setup was used to investigate the curvature-dependence on the interaction of the complement protein C1q with the Fc-domain of antibodies. The antibodies were arranged on two sizes of nanoparticles and a flat surface, and the adsorbed amount of IgG and C1q was determined using Surface Plasmon Resonance and Quartz Crystal Microbalance. There was no difference in adsorption between the two nanoparticles; however, more than 6 times higher amounts per area C1q were found to interact with IgG on a flat surface compared to nanoparticles.
Last, a new method for crosslinking the soft protein corona to the hard corona was developed, which enabled characterisation of the soft protein corona via gel electrophoresis and mass spectrometry in a collaborative project. One of the highly enriched proteins in the soft protein corona was apolipoprotein H, whose interaction with nanoparticles was investigated with surface plasmon resonance using the setup from the first study. Next, the importance of the soft corona proteins in regards to cell uptake was investigated, and a new project on protein coronas formed from different species was initiated.
Together, these new methods help develop the field of nanoparticle-protein interactions, and the results obtained using them give interesting insights that may help preparing nanoparticles for improved drug delivery.
Original languageEnglish
PublisherAarhus Universitet
Number of pages234
Publication statusPublished - Nov 2019

Note re. dissertation

Defence date: 21-11-2019

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ID: 167275374