Magnetic Particle Imaging of Magnetoendosymbionts for Cellular Control

ORAL  · Invited

Abstract

Magnetic Particle Imaging (MPI) is a tracer-based modality that quantitatively maps magnetic nanoparticles with exceptional sensitivity and zero tissue background. Unlike MRI, MPI directly detects the nonlinear magnetization response of superparamagnetic tracers, providing quantitative information on particle concentration, localization, and dynamics. We are extending the reach of this physical imaging method into the domain of cellular engineering by developing magnetoendosymbionts—genetically engineered intracellular organisms that biomineralize magnetic nanoparticles and function as living magnetic transducers within mammalian cells. These magnetoendosymbionts generate biogenic magnetite cores that serve as intrinsic MPI tracers, enabling precise tracking of cellular populations in vivo. Beyond imaging, their magnetic properties allow controlled energy conversion under oscillating magnetic fields. By tuning field amplitude and frequency, we achieve nanoscale magnetothermal heating sufficient to actuate temperature-sensitive genetic switches, providing remote, reversible control over gene expression and cellular behavior. This integrated approach unites the physics of magnetic nanoparticle relaxation with the biological principles of symbiosis and genetic regulation, creating a platform for magnetically addressable living systems. MPI provides quantitative readouts of magnetoendosymbiont distribution and activity, while magnetothermal actuation enables on-demand modulation of cellular programs such as differentiation or therapeutic protein production. The convergence of magnetic imaging, energy transduction, and cellular engineering establishes a foundation for closed-loop control of biological function using purely physical inputs. This work illustrates how principles of magnetic particle physics and non-equilibrium energy transfer can be harnessed to interrogate and direct living matter, opening a new frontier in bio-integrated magnetism and the physical control of cell-based therapeutics.

*This work has been supported, in part, by the James and Kathleen Cornelius Endowment and a NSF Grant (EAGER: Magnetothermal Control of Cell Fates and Function, number MCB2200991)

Publication: Wang, P, Goodwill, PW, Pandit, P, Gaudet, J, Ross, A, Wang, J, Yu, E, Hensley, DW, Doyle, TC, Contag, CH, Conolly, S, Moore, A (2018) Magnetic particle imaging of islet transplantation in the liver and under the kidney capsule in mouse models. Quant Imaging Med Surg 8(2): 114-122. PMCID: PMC5891680

Brewer, KD, Spitler, R, Lee, KR, Chan, AC, Barrozo, JC, Wakeel, A, Foote, CS, Machtaler, S, Rioux, J, Willmann, JK, Chakraborty, P, Rice, BW, Contag, CH, Bell, CB III, Rutt, BK (2018) Characterization of Magneto-Endosymbionts as MRI Cell Labeling and Tracking Agents. Mol Imag Biol 20(1): 66-73. PMCID: PMC5730509

Lee, KR, Wakeel, A, Chakraborty, P, Foote, CS, Kajiura, L, Barrozo, JC, Chan, AC, Bazarov, AV, Spitler, R, Kutny, PM, Denegre, JM, Taft, RA, Seemann, J, Rice, BW, Contag, CH, Rutt, B. K, Bell, CB, III (2018) Cell labeling with magneto-endosymbionts and the dissection of the subcellular location, fate, and host cell interactions. Mol Imag Biol 20(1): 55-64 PMCID: PMC5736464

Makela AV, Gaudet JM, Schott MA, Sehl OC, Contag CH, Foster PJ. (2020) Magnetic particle imaging of macrophages associated with cancer: filling the voids left by iron-based magnetic resonance imaging. Mol. Imaging and Biol. 22(4): 958-968.

Makela AV, Schott MA, Madsen CS, Greeson EM, Contag CH (2022) Magnetic particle imaging of magnetotactic bacteria as living contrast agents is improved by altering magnetosome arrangement. Nano Lett. 22(12):46630-46639 doi: 10.1021/acs.nanolett.1c05042. Online ahead of print. PMID: 35686930

Makela, AV, Schott, MA, Sehl, OC, Gevaert, JJ, Foster, PJ, Contag, CH (2022) Tracking the fates of iron-labeled tumor cells in vivo using magnetic particle imaging. Nanoscale Adv. 4(17): 3617-3623 bioRxiv 2021.10.06.463387; doi: https://doi.org/10.1101/2021.10.06.463387

Greeson, EM, Madsen, CS, Makela, AV, Contag, CH (2022) Magnetothermal control of temperature-sensitive repressors in superparamagnetic iron nanoparticle-coated Bacillus subtilis. ACS Nano. 16(10): 16699-16712. bioRxiv 2022.06.18.496685; doi: https://doi.org/10.1101/2022.06.18.496685

Nigam S, Mohapatra J, Makela AV, Hayat H, Rodriguez JM, Sun A, Kenyon E, Redman NA, Spence D, Jabin G, Gu B, Ashry M, Sempere LF, Mitra A, Li J, Chen J, Wei GW, Bolin S, Etchebarne B, Liu JP, Contag CH, Wang P. (2024) Shape anisotropy-governed high-performance nanomagnetosol for in vivo magnetic particle imaging of lungs. Small. 20(5):e2305300. doi: 10.1002/smll.202305300. Epub ahead of print. PMID: 37735143.

Toomajian, VA, Tundo, A. Ural, EE, Greeson, EM, Contag, CH, Makela, AV (2024) Magnetic particle imaging reveals that iron-labeled extracellular vesicles accumulate in brains of mice with metastases. bioRxiv 2024.03.12.584146; doi: https://doi.org/10.1101/2024.03.12.584146. ACS Appl Mater Interfaces. 16(24): 30860-73I. doi: 10.1021/acsami.4c04920. PMID: 38860682

Makela AV, Gaudet, JM, Murrell, DH, Mansfield, JR, Wintermark, M, Contag, CH (2021) Mind over magnets - How magnetic particle imaging is changing the way we think about the future of neuroscience. Neurosci 22(4): 958-968.

Wang, J, Xing, Y, Ngatio, M, Bies, P, Xu, LL, Xing, L, Zarea, A, Makela, A, Contag, CH, Li, J (2025) Engineering magnetotactic bacteria as medical microrobots. Adv. Mat. 37(27):e2416966.
DOI : 10.1002/adma.202416966

Presenters

  • Christopher Contag

    • Michigan State University

Authors

  • Christopher Contag

    • Michigan State University