Tuning bacterial magnetosomes for biomedical applications by genetic display of peptide arrays

Magnetic nanoparticles are of increasing importance for many applications in the (bio)medical field, for instance as agents for magnetic hyperthermia or imaging techniques. [1]. A promising alternative to chemically synthesized nanoparticles are magnetosomes biomineralized by magnetotactic bacteria. In the alphaproteobacterium Magnetospirillum gryphiswaldense they consist of a monocrystalline magnetite core enveloped by a biological membrane consisting of phospholipids and a set of magnetosome-specific proteins. Due to their strictly genetically regulated biosynthesis, magnetosomes are accessible to genetic engineering techniques for their functionalization, and exhibit characteristics that can hardly be achieved by chemical synthesis [2].

Utilizing abundant magnetosome proteins as anchors, we explored the display of artificial peptides on the magnetosome membrane to increase the particles" biocompatibility and to shield potentially toxic bacterial components. For this purpose, multiple arrays of the tripeptides GSA and PAS and Protein G-derived domains capable of binding Albumins and antibodies, were expressed as fusions to the magnetosome membrane protein MamC. Upon incubation with serum proteins, protein corona formation was observed, which was up to ten-fold higher compared to the wildtype as determined by ELISA and electron microscopy. The genetic introduction of a TEV protease cleavage site enabled the controlled removal of both the proteins expressed on the magnetosome surface as well as the adsorbed corona. The peptide array decorated magnetosomes were shown to be biocompatible when incubated with mammalian cells, and cell viability was kept stable upon prolonged incubation when enveloped by a protein corona. Furthermore, we expect reduced endotoxicity of the particles due to shielding effect of the corona, which is currently tested.

Thus, genetic engineering might not only provide a powerful tool to modify the magnetosome surface properties, but also to improve the biocompatibility for future in vivo applications.

[1] Berry C. C., Curtis A. S., J. Phys. D: Appl. Phys., 2003, 36, R198

[2] Uebe R., Schüler, D., Nat. Rev. Microbiol. 2016, 14, 621