Genetically Controlled Magnetic Nanocompartments for Cell Manipulation - Better Than Ferritin?

Maria V. Efremova^1,2,3, Felix Sigmund^1,2, Silviu-Vasile Bodea^1,2, Irina Beer¹, Maxim A. Abakumov^4,5, Thomas Feggeler⁶, Hendrik Ohldag⁶, Ralf Meckenstock⁷, Natalia Ivleva¹, Ulf Wiedwald⁷, Gil G. Westmeyer^1,2

¹Technical University of Munich, Munich, Germany
²Helmholtz Zentrum München, Neuherberg, Germany
³Eindhoven University of Technology, Eindhoven, Netherlands
⁴Russian National Research Medical University, Moscow, Russia
⁵National University of Science and Technology «MISIS», Moscow, Russia
⁶Advanced Light Source, Lawrence Berkeley National Laboratory, Berkeley, United States
⁷University of Duisburg-Essen, Duisburg, Germany

Using commercially available columns for magnet-assisted cell sorting, we isolated a small fraction of mammalian HEK293T cells grown in a Fe-rich medium and expressing spherical nanoreactors called encapsulins (Sigmund et al., ACS Nano 2019, Efremova et al., Pharmaceutics 2021). The latter represent ginormous analogs of ferritins and naturally occur in bacteria, e.g., Quasibacillus thermotolerans. Encapsulins enable the biomineralization of up to 60000 iron atoms inside their cavity, which is ten times higher than ferritins. TEM and EDX revealed that each sorted cell contained 30±3 nm-sized iron oxide nanoparticles, while XAS and Raman microspectroscopy pointed towards Fe₂O₃ stoichiometry. VSM and FMR proved the ferrimagnetic response of the sorted cells at 5-250K, which corresponds to the maghemite-like (γ-Fe₂O₃) phase rather than to the antiferromagnetic ferrihydrite in ferritins. Finally, we demonstrated that the sorted cells could be manipulated by magnetic gradient fields, making encapsulins a modern tool for the magnetism-driven actuation and imaging of mammalian cells.

We acknowledge the support of an Alexander von Humboldt Research Fellowship for Postdoctoral Researchers, an Add-on Fellowship for Interdisciplinary Life Science by the Joachim Herz Foundation (M.E.), as well as an RSF grant number 19-45-06302 and the Helmholtz-RSF Joint Research Group (HRSF0064).