Ultraparamagnetic cells formed through intracellular oxidation and chelation of paramagnetic iron
Making cells magnetic is a long‐standing goal of chemical biology, aiming to enable the separation of cells from complex biological samples and their visualization in vivo using magnetic resonance imaging (MRI). Previous efforts towards this goal, focused on engineering cells to biomineralize superparamagnetic or ferromagnetic iron oxides, have been largely unsuccessful due to the stringent required chemical conditions. Here, we introduce an alternative approach to making cells magnetic, focused on biochemically maximizing cellular paramagnetism. We show that a novel genetic construct combining the functions of ferroxidation and iron chelation enables engineered bacterial cells to accumulate iron in "ultraparamagnetic" macromolecular complexes, allowing these cells to be trapped with magnetic fields and imaged with MRI in vitro and in vivo. We characterize the properties of these cells and complexes using magnetometry, nuclear magnetic resonance, biochemical assays, and computational modeling to elucidate the unique mechanisms and capabilities of this paramagnetic concept.
© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. Accepted manuscript online: 08 August 2018; Manuscript accepted: 07 August 2018; Manuscript revised: 06 August 2018; Manuscript received: 30 April 2018. We thank Matthew Chalkley for assistance with Mossbauer spectroscopy, Dr. Paul Oyala for assistance with magnetic resonance and Dr. Michael Tyszka for helpful discussions. This research was supported by the W.M. Keck Foundation, the Dana Foundation and the Burroughs Wellcome Fund. P.R. was supported by a National Science Foundation Graduate Research Fellowship and a National Institutes of Health training grant (5T32GM112592). Related research in the Shapiro laboratory is also supported by the Heritage Medical Research Institute, the David and Lucille Packard Foundation and the Pew Charitable Trusts. The authors declare no conflict of interest.
Supplemental Material - anie201805042-s1-ramesh_angewandte_final_supporting_information_v3.pdf
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