Ultraparamagnetic Cells Formed through Intracellular Oxidation and Chelation of Paramagnetic Iron

Abstract

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.

Medical Micro/Nanorobots in Precision Medicine

“…[126][127][128][129][130][131] More recently, advances in synthetic biology have made possible the ability to enhance the capabilities of the motile microorganism without the use of artificial components. For example, genetically engineered bacteria have been programmed to generate diverse active components, such as magnetic particles, [132,133] gas-filled microstructures, [134,135] therapeutic payloads, [136] or responsive probes. [137] In a nutshell, locally powered microrobots have built-in energy conversion on their active surfaces or exploited the autonomous motility of microorganisms.…”

Engineering E. coli for Magnetic Control and the Spatial Localization of Functions

“…A third approach aimed to magnetize naturally diamagnetic microorganisms or eukaryotic cells by over-expressing iron-storage ferritins or iron-binding proteins inside their cytoplasm. These bacteria could serve as containers favoring the formation of iron-oxide deposits when cells were fed with iron [35][36][37][38][39][40] . These studies showed that mineralized cells contained iron oxide deposits, can be detected using NMR, and can be magnetically sorted.…”

“…One second strategy consisted in building bacterial biohybrid systems either using magnetotactic bacteria carrying cargo-particles, , or reciprocally, using a magnetic field to control the orientation of motile bacteria linked to magnetic beads. , A third approach aimed to magnetize naturally diamagnetic microorganisms or eukaryotic cells by overexpressing iron-storage ferritins or iron-binding proteins inside their cytoplasm. These bacteria could serve as containers favoring the formation of iron-oxide deposits when cells were fed with iron. − These studies showed that mineralized cells containing iron oxide deposits can be detected using NMR and can be magnetically sorted. However, to envision biotechnological applications using mineralized cells, several important challenges still need to be achieved.…”

EngineeringE. colifor magnetic control and the spatial localization of functions

“…A third approach aimed to magnetize naturally diamagnetic microorganisms or eukaryotic cells by over-expressing iron-storage ferritins or iron-binding proteins inside their cytoplasm. These bacteria could serve as containers favoring the formation of iron-oxide deposits when cells were fed with iron [35][36][37][38][39][40] . These studies showed that mineralized cells contained iron oxide deposits, can be detected using NMR, and can be magnetically sorted.…”