bims-mricoa Biomed News
on MRI contrast agents
Issue of 2021–11–07
eleven papers selected by
Merve Yavuz, Bilkent University



  1. J Struct Biol X. 2021 ;5 100052
      Biomineralization is the process of mineral formation by living organisms. One notable example of these organisms is magnetotactic bacteria (MTB). MTB are Gram-negative bacteria that can biomineralize iron into magnetic nanoparticles. This ability allows these aquatic microorganisms to orient themselves according to the geomagnetic field. The biomineralization process takes place in a specialized sub-cellular membranous organelle, the magnetosome. The magnetosome contains a defined set of magnetosome-associated proteins (MAPs) that controls the biomineralization environment, including iron concentration, redox, and pH. Magnetite formation is subjected to a tight regulation within the magnetosome that affects the nanoparticle nucleation, size, and shape, leading to well-defined magnetic properties. The formed magnetite nanoparticles have unique characteristics of a stable, single magnetic domain with narrow size distribution and high crystalline structures, which turned MTB into the subject of interest in multidisciplinary research. This graphical review provides a current overview of iron biomineralization in magnetotactic bacteria, focusing on Alphaproteobacteria. To better understand this complex mechanism, we present the four main steps and the main MAPs participating in the process of magnetosome formation.
    Keywords:  Biomineralization; Iron oxides; Magnetosome; Magnetotactic bacteria
    DOI:  https://doi.org/10.1016/j.yjsbx.2021.100052
  2. Small. 2021 Nov 06. e2104079
      Magnetic nanoparticles (MNPs) have various applications in biomedicine, including imaging, drug delivery and release, genetic modification, cell guidance, and patterning. By combining MNPs with polymers, magnetic nanocomposites (MNCs) with diverse morphologies (core-shell particles, matrix-dispersed particles, microspheres, etc.) can be generated. These MNCs retain the ability of MNPs to be controlled remotely using external magnetic fields. While the effects of these biomaterials on the cell biology are still poorly understood, such information can help the biophysical modulation of various cellular functions, including proliferation, adhesion, and differentiation. After recalling the basic properties of MNPs and polymers, and describing their coassembly into nanocomposites, this review focuses on how polymeric MNCs can be used in several ways to affect cell behavior. A special emphasis is given to 3D cell culture models and transplantable grafts, which are used for regenerative medicine, underlining the impact of MNCs in regulating stem cell differentiation and engineering living tissues. Recent advances in the use of MNCs for tissue regeneration are critically discussed, particularly with regard to their prospective involvement in human therapy and in the construction of advanced functional materials such as magnetically operated biomedical robots.
    Keywords:  magnetic nanoparticles; nanocomposites; polymers; remote control; tissue engineering
    DOI:  https://doi.org/10.1002/smll.202104079
  3. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2021 Nov 01. e1761
      Synthetic cells are engineered vesicles that can mimic one or more salient features of life. These features include directed localization, sense-and-respond behavior, gene expression, metabolism, and high stability. In nanomedicine, many of these features are desirable capabilities of drug delivery vehicles but are difficult to engineer. In this focus article, we discuss where synthetic cells offer unique advantages over nanoparticle and living cell therapies. We review progress in the engineering of the above life-like behaviors and how they are deployed in nanomedicine. Finally, we assess key challenges synthetic cells face before being deployed as drugs and suggest ways to overcome these challenges. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Biology-Inspired Nanomaterials > Lipid-Based Structures.
    Keywords:  synthetic biology; synthetic cells
    DOI:  https://doi.org/10.1002/wnan.1761
  4. Adv Mater. 2021 Nov 06. e2105758
      Demands for next-generation soft and responsive materials have sparked recent interest in the development of shape-changing particles and particle assemblies. Over the last two decades, a variety of mechanisms that drive shape change have been explored and integrated into particulate systems. Through a combination of top-down fabrication and bottom-up synthesis techniques, shape-morphing capabilities extend from the microscale to the nanoscale. Consequently, shape-morphing particles are rapidly emerging in a variety of contexts, including photonics, microfluidics, microrobotics, and biomedicine. Herein, the key mechanisms and materials that facilitate shape changes of microscale and nanoscale particles are discussed. Recent progress in the applications made possible by these particles is summarized, and perspectives on their promise and key open challenges in the field are discussed.
    Keywords:  colloids; reconfiguration; robotics; self-assembly; shape-changing particles; soft materials; stimuli-responsive materials
    DOI:  https://doi.org/10.1002/adma.202105758
  5. J Chromatogr A. 2021 Oct 22. pii: S0021-9673(21)00762-7. [Epub ahead of print]1659 462638
      Enzymes possess a highly specific affinity toward their substrates. In this study, an enzyme-based biological method was established for chiral discrimination of D/L-tryptophan (Trp). The polydopamine modified magnetic particles (PDA@Fe3O4) were prepared for immobilization of the genetically engineered bacterium Escherichia coli (E. coli) DH5α. The bacteria-magnetic particles conjugates (bacteria@PDA@Fe3O4) demonstrate excellent chiral discrimination performance toward D/L-Trp at pH 7.0 and 45 °C. The investigation for the principle exhibits that the immobilized E. coli DH5α can produce tryptophanase, and the enzyme can selectively recognize and degrade L-Trp. The Michaelis constant of tryptophanase produced by bacteria@PDA@Fe3O4 was measured to be 25.7 µg mL-1. This method avoids the purification of tryptophanase and unlocks the potential of bacteria modified magnetic particles for chiral discrimination of racemic tryptophan.
    Keywords:  Bacteria; Enantioseparation; Magnetic particles; Polydopamine; Tryptophan
    DOI:  https://doi.org/10.1016/j.chroma.2021.462638
  6. Curr Opin Biomed Eng. 2021 Dec;pii: 100300. [Epub ahead of print]20
      There is great interest in developing gene therapies for many disease indications, including cancer. However, successful delivery of nucleic acids to tumor cells is a major challenge, and in vivo efficacy is difficult to predict. Cancer theranostics is an approach combining anti-tumor therapy with imaging or diagnostic capabilities, with the goal of monitoring successful delivery and efficacy of a therapeutic agent in a tumor. Successful theranostics must maintain a high degree of anticancer targeting and efficacy while incorporating high-contrast imaging agents that are nontoxic and compatible with clinical imaging modalities. This review highlights recent advancements in theranostic strategies, including imaging technologies and genetic engineering approaches. Graphical Abstract.
    DOI:  https://doi.org/10.1016/j.cobme.2021.100300
  7. Biotechnol Biofuels. 2021 Nov 04. 14(1): 212
       BACKGROUND: CO2 valorization is one of the effective methods to solve current environmental and energy problems, in which microbial electrosynthesis (MES) system has proved feasible and efficient. Cupriviadus necator (Ralstonia eutropha) H16, a model chemolithoautotroph, is a microbe of choice for CO2 conversion, especially with the ability to be employed in MES due to the presence of genes encoding [NiFe]-hydrogenases and all the Calvin-Benson-Basham cycle enzymes. The CO2 valorization strategy will make sense because the required hydrogen can be produced from renewable electricity independently of fossil fuels.
    MAIN BODY: In this review, synthetic biology toolkit for C. necator H16, including genetic engineering vectors, heterologous gene expression elements, platform strain and genome engineering, and transformation strategies, is firstly summarized. Then, the review discusses how to apply these tools to make C. necator H16 an efficient cell factory for converting CO2 to value-added products, with the examples of alcohols, fatty acids, and terpenoids. The review is concluded with the limitation of current genetic tools and perspectives on the development of more efficient and convenient methods as well as the extensive applications of C. necator H16.
    CONCLUSIONS: Great progress has been made on genetic engineering toolkit and synthetic biology applications of C. necator H16. Nevertheless, more efforts are expected in the near future to engineer C. necator H16 as efficient cell factories for the conversion of CO2 to value-added products.
    Keywords:  Biomanufacturing; CO2 conversion; Cupriviadus necator H16; Metabolic engineering; Ralstonia eutropha H16; Synthetic biology
    DOI:  https://doi.org/10.1186/s13068-021-02063-0
  8. ACS Synth Biol. 2021 Nov 02.
      Filamentous fungi are highly productive cell factories, often used in industry for the production of enzymes and small bioactive compounds. Recent years have seen an increasing number of synthetic-biology-based applications in fungi, emphasizing the need for a synthetic biology toolkit for these organisms. Here we present a collection of 96 genetic parts, characterized in Penicillium or Aspergillus species, that are compatible and interchangeable with the Modular Cloning system. The toolkit contains natural and synthetic promoters (constitutive and inducible), terminators, fluorescent reporters, and selection markers. Furthermore, there are regulatory and DNA-binding domains of transcriptional regulators and components for implementing different CRISPR-based technologies. Genetic parts can be assembled into complex multipartite assemblies and delivered through genomic integration or expressed from an AMA1-sequence-based, fungal-replicating shuttle vector. With this toolkit, synthetic transcription units with established promoters, fusion proteins, or synthetic transcriptional regulation devices can be more rapidly assembled in a standardized and modular manner for novel fungal cell factories.
    Keywords:  Modular Cloning; filamentous fungi; hybrid transcription factor; inducible promoter; synthetic biology toolkit; transcriptional regulation
    DOI:  https://doi.org/10.1021/acssynbio.1c00260
  9. Adv Sci (Weinh). 2021 Oct 31. e2102545
      Damaged skin cannot prevent harmful bacteria from invading tissues, causing infected wounds and even serious tissue damage. Traditional treatments can not only kill pathogenic bacteria, but also suppress the growth of beneficial bacteria, thus destroying the balance of the damaged skin microbial ecosystem. Here, a living bacterial hydrogel scaffold is reported that accelerates infected wound healing through beneficial bacteria secreting antibacterial substances. Lactobacillus reuteri, a common probiotic, is encapsulated in hydrogel microspheres by emulsion polymerization and further immobilized in a hydrogel network by covalent cross-linking of methacrylate-modified hyaluronic acid. Owing to light-initiated crosslinking, the hydrogel dressing can be generated in situ at the wound site. This hydrogel scaffold not only protects bacteria from immune system attack, but also prevents bacteria from escaping into the local environment, thus avoiding potential threats. Both in vitro and in vivo experiments show that it has excellent ability against harmful bacteria and anti-inflammatory capabilities, promoting infected wound closure and new tissue regeneration. This work may open up new avenues for the application of living bacteria in the clinical management of infected wounds.
    Keywords:  antibacterial hydrogels; hydrogel microspheres; living bacteria; microbial competition; wound healing
    DOI:  https://doi.org/10.1002/advs.202102545
  10. ACS Synth Biol. 2021 Nov 05.
      We investigated the scalability of a previously developed growth switch based on external control of RNA polymerase expression. Our results indicate that, in liter-scale bioreactors operating in fed-batch mode, growth-arrested Escherichia coli cells are able to convert glucose to glycerol at an increased yield. A multiomics quantification of the physiology of the cells shows that, apart from acetate production, few metabolic side effects occur. However, a number of specific responses to growth slow-down and growth arrest are launched at the transcriptional level. These notably include the downregulation of genes involved in growth-associated processes, such as amino acid and nucleotide metabolism and translation. Interestingly, the transcriptional responses are buffered at the proteome level, probably due to the strong decrease of the total mRNA concentration after the diminution of transcriptional activity and the absence of growth dilution of proteins. Growth arrest thus reduces the opportunities for dynamically adjusting the proteome composition, which poses constraints on the design of biotechnological production processes but may also avoid the initiation of deleterious stress responses.
    Keywords:  Escherichia coli; bioinformatics; growth switch; metabolic engineering; multiomics data integration; synthetic circuit
    DOI:  https://doi.org/10.1021/acssynbio.1c00115
  11. J Mater Chem B. 2021 Nov 03.
      Ferroptosis, a cell death pathway involving iron-related generation of lipid hydroperoxides for achieving incredible tumor suppression, has reignited the hope of chemotherapy in tumor treatment in the past decade. With extensive research studies, various bioactive proteins and cellular pathways have been demonstrated to regulate the occurrence and development of ferroptosis. The gradually established ferroptotic regulatory network is conducive to find effective proteins from a holistic perspective and guides better designs for future ferroptotic tumor therapies. The first section of this review summarizes the recent advances in ferroptotic regulatory mechanisms of proteins and attempts to clarify their latent function in the ferroptotic regulatory network. Second, the existing protein-mediated ferroptotic tumor nanotherapeutic strategies were reviewed, including the protein-mediated iron supplement, cell membrane transporter inhibition, glutathione peroxidase 4 interference, glutathione depletion, bioenzyme-mediated reactive oxygen species generation, heat shock protein inhibition, and tumor-overexpressed protein-triggered drug release for ferroptotic therapy. Finally, the future expectations and challenges of ferroptotic tumor nanotherapeutics for clinical cancer therapy are highlighted.
    DOI:  https://doi.org/10.1039/d1tb01289d