bims-mricoa Biomed News
on MRI contrast agents
Issue of 2022–09–25
seven papers selected by
Merve Yavuz, Bilkent University
  1. The Magnetosome Protein, Mms6 from Magnetospirillum magneticum Strain AMB-1, Is a Lipid-Activated Ferric Reductase.
  2. Prussian Blue Staining to Visualize Iron Oxide Nanoparticles.
  3. Degradable silk-based soft actuators with magnetic responsiveness.
  4. Cell Rover-a miniaturized magnetostrictive antenna for wireless operation inside living cells.
  5. Bioselectivity of silk protein-based materials and their bio-inspired applications.
  6. Silk fibroin films with embedded magnetic nanoparticles: evaluation of the magneto-mechanical stimulation effect on osteogenic differentiation of stem cells.
  7. Kinetics of nanoparticle uptake into and distribution in human cells.
  1. Int J Mol Sci. 2022 Sep 07. pii: 10305. [Epub ahead of print]23(18):
    The Magnetosome Protein, Mms6 from Magnetospirillum magneticum Strain AMB-1, Is a Lipid-Activated Ferric Reductase.
    Dilini Singappuli-Arachchige, Shuren Feng, Lijun Wang, Pierre E Palo, Samuel O Shobade, Michelle Thomas, Marit Nilsen-Hamilton.
      Magnetosomes of magnetotactic bacteria consist of magnetic nanocrystals with defined morphologies enclosed in vesicles originated from cytoplasmic membrane invaginations. Although many proteins are involved in creating magnetosomes, a single magnetosome protein, Mms6 from Magnetospirillum magneticum strain AMB-1, can direct the crystallization of magnetite nanoparticles in vitro. The in vivo role of Mms6 in magnetosome formation is debated, and the observation that Mms6 binds Fe3+ more tightly than Fe2+ raises the question of how, in a magnetosome environment dominated by Fe3+, Mms6 promotes the crystallization of magnetite, which contains both Fe3+ and Fe2+. Here we show that Mms6 is a ferric reductase that reduces Fe3+ to Fe2+ using NADH and FAD as electron donor and cofactor, respectively. Reductase activity is elevated when Mms6 is integrated into either liposomes or bicelles. Analysis of Mms6 mutants suggests that the C-terminal domain binds iron and the N-terminal domain contains the catalytic site. Although Mms6 forms multimers that involve C-terminal and N-terminal domain interactions, a fusion protein with ubiquitin remains a monomer and displays reductase activity, which suggests that the catalytic site is fully in the monomer. However, the quaternary structure of Mms6 appears to alter the iron binding characteristics of the C-terminal domain. These results are consistent with a hypothesis that Mms6, a membrane protein, promotes the formation of magnetite in vivo by a mechanism that involves reducing iron.
    Keywords:  Mms6; bicelles; ferric reductase; lipid
    DOI:  https://doi.org/10.3390/ijms231810305
  2. Methods Mol Biol. 2023 ;2566 321-332
    Prussian Blue Staining to Visualize Iron Oxide Nanoparticles.
    Valeria Bitonto, Francesca Garello, Arnaud Scherberich, Miriam Filippi.
      Iron deposits in cells and tissues can be detected by ex vivo histological examination through the Prussian blue (PB) staining. This practical, inexpensive, and highly sensitive technique involves the treatment of fixed tissue sections and cells with acid solutions of ferrocyanides that combine with ferric ion forming a bright blue pigment (i.e., ferric ferrocyanide). The staining can be applied to visualize iron oxide nanoparticles (IONPs), versatile magnetic nanosystems that are used in various biomedical applications and whose localization is usually required at a higher resolution than that enabled by in vivo tracking techniques.
    Keywords:  Ferric iron; Histology; Perls’ staining; Superparamagnetic iron oxide nanoparticles
    DOI:  https://doi.org/10.1007/978-1-0716-2675-7_26
  3. J Mater Chem B. 2022 Sep 21.
    Degradable silk-based soft actuators with magnetic responsiveness.
    Niping Deng, Jinghang Li, Hao Lyu, Ruochuan Huang, Haoran Liu, Chengchen Guo.
      Soft actuators with stimuli-responsiveness have great potential in biomedical applications such as drug delivery and minimally invasive surgery. In this study, protein-based soft actuators with magnetic actuation are fabricated using naturally occurring silk proteins and synthesized Fe3O4 magnetic nanoparticles (NPs). Briefly, magnetic silk films are first prepared by solution casting of a mixture containing silk proteins, synthesized Fe3O4 NPs, and glycerol. The molecular structures of the magnetic silk films are characterized by FTIR spectroscopy, which show that the β-sheet content in the films is about 20%. The mechanical tests show that the magnetic silk films can be stretched to over 200% under wet conditions and Young's modulus is estimated to be 4.89 ± 0.69 MPa, matching the stiffness of soft tissues. Furthermore, the enzymatic degradability, good biocompatibility, and in vivo X-ray visibility of the films are demonstrated by the in vitro enzymatic degradation test, in vivo biocompatibility test, and micro-CT imaging, respectively. Degradable silk-based soft actuators with magnetic responsiveness are successfully prepared by thermal forming or plastic molding of the magnetic silk films. The fabricated soft actuators can be actuated and move with precise locomotive gaits in solutions using a magnet. In addition, the retention of the soft actuators and localized drug delivery in gastrointestinal tracts by attaching a magnet to the abdominal skin are demonstrated using model systems. The degradable silk-based soft actuators provide many opportunities for improving current therapeutic strategies in biomedicine.
    DOI:  https://doi.org/10.1039/d2tb01328b
  4. Nat Commun. 2022 Sep 22. 13(1): 5210
    Cell Rover-a miniaturized magnetostrictive antenna for wireless operation inside living cells.
    Baju Joy, Yubin Cai, David C Bono, Deblina Sarkar.
      An intracellular antenna can open up new horizons for fundamental and applied biology. Here, we introduce the Cell Rover, a magnetostrictive antenna which can operate wirelessly inside a living cell and is compatible with 3D biological systems. It is sub-mm in size, acoustically actuated by an AC magnetic field and resonantly operated at low MHz frequencies, which is ideal for living systems. We developed an injection scheme involving non-uniform magnetic fields for intracellular injection of the Cell Rovers and demonstrated their operation in fully opaque, stage VI Xenopus oocytes, for which real-time imaging with conventional technologies is challenging. We also show that they provide a pathway for multiplexing applications to individually address multiple cells or to tune to more than one antenna within the same cell for versatile functionalities. This technology forms the foundation stone that can enable the integration of future capabilities such as smart sensing, modulation as well as energy harvesting to power in-cell nanoelectronic computing and can potentially bring the prowess of information technology inside a living cell. This could lead to unprecedented opportunities for fundamental understanding of biology as well as diagnostics and therapeutics.
    DOI:  https://doi.org/10.1038/s41467-022-32862-4
  5. Beilstein J Nanotechnol. 2022 ;13 902-921
    Bioselectivity of silk protein-based materials and their bio-inspired applications.
    Hendrik Bargel, Vanessa T Trossmann, Christoph Sommer, Thomas Scheibel.
      Adhesion to material surfaces is crucial for almost all organisms regarding subsequent biological responses. Mammalian cell attachment to a surrounding biological matrix is essential for maintaining their survival and function concerning tissue formation. Conversely, the adhesion and presence of microbes interferes with important multicellular processes of tissue development. Therefore, tailoring bioselective, biologically active, and multifunctional materials for biomedical applications is a modern focus of biomaterial research. Engineering biomaterials that stimulate and interact with cell receptors to support binding and subsequent physiological responses of multicellular systems attracted much interest in the last years. Further to this, the increasing threat of multidrug resistance of pathogens against antibiotics to human health urgently requires new material concepts for preventing microbial infestation and biofilm formation. Thus, materials exhibiting microbial repellence or antimicrobial behaviour to reduce inflammation, while selectively enhancing regeneration in host tissues are of utmost interest. In this context, protein-based materials are interesting candidates due to their natural origin, biological activity, and structural properties. Silk materials, in particular those made of spider silk proteins and their recombinant counterparts, are characterized by extraordinary properties including excellent biocompatibility, slow biodegradation, low immunogenicity, and non-toxicity, making them ideally suited for tissue engineering and biomedical applications. Furthermore, recombinant production technologies allow for application-specific modification to develop adjustable, bioactive materials. The present review focusses on biological processes and surface interactions involved in the bioselective adhesion of mammalian cells and repellence of microbes on protein-based material surfaces. In addition, it highlights the importance of materials made of recombinant spider silk proteins, focussing on the progress regarding bioselectivity.
    Keywords:  antifouling; bacteriostatic; biofouling; bioselective cell adhesion; spider silk protein
    DOI:  https://doi.org/10.3762/bjnano.13.81
  6. Nanoscale. 2022 Sep 23.
    Silk fibroin films with embedded magnetic nanoparticles: evaluation of the magneto-mechanical stimulation effect on osteogenic differentiation of stem cells.
    Lucia Del Bianco, Federico Spizzo, Yuejiao Yang, Gabriele Greco, Maria Laura Gatto, Gianni Barucca, Nicola M Pugno, Antonella Motta.
      We report about a biomaterial in the form of film ∼10 μm thick, consisting of a silk fibroin matrix with embedded iron oxide superparamagnetic nanoparticles, for prospective applications as bioactive coating in regenerative medicine. Films with different load of magnetic nanoparticles are produced (nanoparticles/silk fibroin nominal ratio = 5, 0.5 and 0 wt%) and the structural, mechanical and magnetic properties are studied. The nanoparticles form aggregates in the silk fibroin matrix and the film stiffness, as tested by nanoindentation, is spatially inhomogeneous, but the protein structure is not altered. In vitro biological tests are carried out on human bone marrow-derived mesenchymal stem cells cultured on the films up to 21 days, with and without an applied static uniform magnetic field. The sample with the highest nanoparticles/silk fibroin ratio shows the best performance in terms of cell proliferation and adhesion. Moreover, it promotes a faster and better osteogenic differentiation, particularly under magnetic field, as indicated by the gene expression level of typical osteogenic markers. These findings are explained in light of the results of the physical characterization, combined with numerical calculations. It is established that the applied magnetic field triggers a virtuous magneto-mechanical mechanism in which dipolar magnetic forces between the nanoparticle aggregates give rise to a spatial distribution of mechanical stresses in the silk fibroin matrix. The film with the largest nanoparticle load, under cell culture conditions (i.e. in aqueous environment), undergoes matrix deformations large enough to be sensed by the seeded cells as mechanical stimuli favoring the osteogenic differentiation.
    DOI:  https://doi.org/10.1039/d2nr03167a
  7. Nanoscale Adv. 2021 Apr 20. 3(8): 2196-2212
    Kinetics of nanoparticle uptake into and distribution in human cells.
    Christoffer Åberg.
      Whether one wishes to optimise drug delivery using nano-sized carriers or avoid hazard posed by engineered nanomaterials, the kinetics of nanoparticle uptake into human cells and their subsequent intracellular distribution is key. Unique properties of the nanoscale implies that such nanoparticles are taken up and trafficked in a different fashion compared to molecular species. In this review, we discuss in detail how to describe the kinetics of nanoparticle uptake and intracellular distribution, using previous studies for illustration. We also cover the extracellular kinetics, particle degradation, endosomal escape and cell division, ending with an outlook on the future of kinetic studies.
    DOI:  https://doi.org/10.1039/d0na00716a
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