title: Genetically programmed superparamagnetic behavior of mammalian cells.
abstract: Although magnetic fields and paramagnetic inorganic materials were abundant on planet earth during the entire evolution of living species the interaction of organisms with these physical forces remains a little-understood phenomenon. Interestingly, rather than being genetically encoded, organisms seem to accumulate and take advantage of inorganic nanoparticles to sense or react to magnetic fields. Using a synthetic biology-inspired approach we have genetically programmed mammalian cells to show superparamagnetic behavior. The combination of ectopic production of the human ferritin heavy chain 1 (hFTH1), engineering the cells for expression of an iron importer, the divalent metal ion transferase 1 (DMT1) and the design of an iron-loading culture medium to maximize cellular iron uptake enabled efficient iron mineralization in intracellular ferritin particles and conferred superparamagnetic behavior to the entire cell. When captured by a magnetic field the superparamagnetic cells reached attraction velocities of up to 30 μm/s and could be efficiently separated from complex cell mixtures using standard magnetic cell separation equipment. Technology that enables magnetic separation of genetically programmed superparamagnetic cells in the absence of inorganic particles could foster novel opportunities in diagnostics and cell-based therapies.
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, CH-4058 Basel, Switzerland.
authors.forename: Taeuk
authors.initials: T
authors.lastname: Kim
authors.forename: David
authors.initials: D
authors.lastname: Moore
authors.forename: Martin
authors.initials: M
authors.lastname: Fussenegger
mesh_terms: D027682:Cation Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002469:Cell Separation / Q000379:methods*; D002470:Cell Survival; D003470:Culture Media / Q000737:chemistry; D005293:Ferritins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005818:Genetic Engineering / Q000379:methods*; D057809:HEK293 Cells; D006801:Humans; D042541:Intracellular Space; D007501:Iron / Q000378:metabolism; D060526:Magnetic Fields; D008280:Magnetics / Q000379:methods*; D010088:Oxidoreductases; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D058615:Synthetic Biology / Q000379:methods; D000099236:Solute Carrier Family 11, Member 2
chemical_list: D027682:Cation Transport Proteins; D003470:Culture Media; D005293:Ferritins; D007501:Iron; D010088:Oxidoreductases; D011993:Recombinant Fusion Proteins; D000099236:Solute Carrier Family 11, Member 2; C454461:FTH1 protein, human