Ultraparamagnetic Cells Formed through Intracellular Oxidation and Chelation of Paramagnetic Iron

Ramesh, Pradeep; Hwang, Son‐Jong; Davis, Hunter C.; Lee‐Gosselin, Audrey; Bharadwaj, Vivek; English, Max A; Sheng, Jenny; Iyer, Vasant; Shapiro, Mikhail G.

doi:10.1002/ange.201805042

Cited by 4 publications

(3 citation statements)

References 32 publications

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“…While the current study demonstrated MR imaging of E. coli (F + ) and V. cholerae cells, DP1-phage may in principle be engineered to noninvasively monitor different bacterial targets by tuning one of the four phage coat proteins (keeping pVIII for DP1 fusion) to incorporate receptorbinding proteins from native phages with tropism towards the desired bacterial strain 30 . The present work also established preliminary proof-of-principle for in vivo imaging of bacteria pre-labeled with DP1phage, which may be useful for cell tracking applications involving the use of bacteria as live-cell therapeutics, especially if genetic modification of the bacterial strain to express reporter genes for noninvasive imaging [31][32][33] is not desirable or possible. In situ detection of pathogenic or commensal microorganisms in their animal host would however require DP1-phage to be delivered in vivo.…”

Section: Discussionmentioning

confidence: 80%

A genetically engineered phage-based nanomaterial for detecting bacteria with magnetic resonance imaging

Borg

Ozbakir

et al. 2022

Preprint

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The ability to noninvasively detect bacteria at any depth inside opaque tissues has important applications ranging from infection diagnostics to tracking therapeutic microbes in their mammalian host. Current examples of probes for detecting bacteria with strain-type specificity are largely based on optical dyes, which cannot be used to examine bacteria in deep tissues due to the physical limitation of light scattering. Here, we describe a new biomolecular probe for visualizing bacteria in a cell-type specific fashion using magnetic resonance imaging (MRI). The probe is based on a peptide that selectively binds manganese and is attached in high numbers to the capsid of filamentous phage. By genetically engineering phage particles to display this peptide, we are able to bring manganese ions to specific bacterial cells targeted by the phage, thereby producing MRI contrast. We show that this approach allows MRI-based detection of targeted E. coli strains while discriminating against non-target bacteria as well as mammalian cells. By engineering the phage coat to display a protein that targets cell surface receptors in V. cholerae, we further show that this approach can be applied to image other bacterial targets with MRI. Finally, as a preliminary example of in vivo applicability, we demonstrate MR imaging of phage-labeled V. cholerae cells implanted subcutaneously in mice. The nanomaterial developed here thus represents a path towards noninvasive detection and tracking of bacteria by combining the programmability of phage architecture with the ability to produce three-dimensional images of biological structures at any arbitrary depth with MRI.

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Section: Discussionmentioning

confidence: 80%

A genetically engineered phage-based nanomaterial for detecting bacteria with magnetic resonance imaging

Borg

Ozbakir

et al. 2022

Preprint

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“…While ferritin nanoparticles may be assembled inside cells with genetic encoding, the ensuing magnetization is much smaller than similarly-sized synthetic nanoparticles, which limits the sensitivity of the clustering mechanism for ferritin-based biosensing. [66] That said, the recent advent of several engineered iron-nucleating proteins with higher per-particle magnetic moments [39,[67][68][69][70] compared to ferritin provides a fresh set of biomolecular templates that could be used to sense dilute analytes based on nanoscale assembly and aggregation. The general feasibility of this approach has already been established by imaging streptavidin in yeast cells engineered to express a hypermagnetic variant of ferritin fused with streptavidin-binding peptides.…”

Section: Discussionmentioning

confidence: 99%

Designing Protein‐Based Probes for Sensing Biological Analytes with Magnetic Resonance Imaging

et al. 2022

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Genetically encoded sensors provide unique advantages for monitoring biological analytes with molecular and cellular-level specificity. While sensors derived from fluorescent proteins represent staple tools in biological imaging, these probes are limited to optically accessible preparations owing to physical curbs on light penetration. In contrast to optical methods, magnetic resonance imaging (MRI) may be used to noninvasively look inside intact organisms at any arbitrary depth and over large fields of view. These capabilities have spurred the development of innovative methods to connect MRI readouts with biological targets using protein-based probes that are in principle genetically encodable. Here, we highlight the stateof-the-art in MRI-based biomolecular sensors, focusing on their physical mechanisms, quantitative characteristics, and biological applications. We also describe how innovations in reporter gene technology are creating new opportunities to engineer MRI sensors that are sensitive to dilute biological targets.

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“…Recent advances in synthetic biology have enabled the enhancement of the capabilities of motile microorganisms without the usage of artificial components, such as programming genetically engineered bacteria to generate diverse, active components, including magnetic particles [128,129], gas-filled microstructures [130,131], therapeutic payloads [132], or responsive probes [133]. The synthetic biological approach, however, is beyond the scope of this work.…”

Section: Bio-hybrid Microswimmersmentioning

confidence: 99%

Fabrication, control, and modeling of robots inspired by flagella and cilia

Lim

Du²,

Lee³

et al. 2022

Bioinspir. Biomim.

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Flagella and cilia are slender structures that serve important functionalities in the microscopic world through their locomotion induced by fluid and structure interaction. With recent developments in microscopy, fabrication, biology, and modeling capability, robots inspired by the locomotion of these organelles in low Reynolds number flow have been manufactured and tested on the micro-and macro-scale, ranging from medical in vivo microbots, microfluidics to macro prototypes. We present an unprecedented collection of modeling theories, control principles, and fabrication methods for flagellated and ciliary robots.

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Ultraparamagnetic Cells Formed through Intracellular Oxidation and Chelation of Paramagnetic Iron

Abstract: Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

Cited by 4 publications

References 32 publications

A genetically engineered phage-based nanomaterial for detecting bacteria with magnetic resonance imaging

A genetically engineered phage-based nanomaterial for detecting bacteria with magnetic resonance imaging

Designing Protein‐Based Probes for Sensing Biological Analytes with Magnetic Resonance Imaging

Fabrication, control, and modeling of robots inspired by flagella and cilia

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