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      Programmed Self-Assembly of a Biochemical and Magnetic Scaffold to Trigger and Manipulate Microtubule Structures

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          Abstract

          Artificial bio-based scaffolds offer broad applications in bioinspired chemistry, nanomedicine, and material science. One current challenge is to understand how the programmed self-assembly of biomolecules at the nanometre level can dictate the emergence of new functional properties at the mesoscopic scale. Here we report a general approach to design genetically encoded protein-based scaffolds with modular biochemical and magnetic functions. By combining chemically induced dimerization strategies and biomineralisation, we engineered ferritin nanocages to nucleate and manipulate microtubule structures upon magnetic actuation. Triggering the self-assembly of engineered ferritins into micrometric scaffolds mimics the function of centrosomes, the microtubule organizing centres of cells, and provides unique magnetic and self-organizing properties. We anticipate that our approach could be transposed to control various biological processes and extend to broader applications in biotechnology or material chemistry.

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          Polyvalent Interactions in Biological Systems: Implications for Design and Use of Multivalent Ligands and Inhibitors

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            Multifunctional magnetic nanoparticles: design, synthesis, and biomedical applications.

            The combination of nanotechnology and molecular biology has developed into an emerging research area: nanobiotechnology. Magnetic nanoparticles are well-established nanomaterials that offer controlled size, ability to be manipulated externally, and enhancement of contrast in magnetic resonance imaging (MRI). As a result, these nanoparticles could have many applications in biology and medicine, including protein purification, drug delivery, and medical imaging. Because of the potential benefits of multimodal functionality in biomedical applications, researchers would like to design and fabricate multifunctional magnetic nanoparticles. Currently, there are two strategies to fabricate magnetic nanoparticle-based multifunctional nanostructures. The first, molecular functionalization, involves attaching antibodies, proteins, and dyes to the magnetic nanoparticles. The other method integrates the magnetic nanoparticles with other functional nanocomponents, such as quantum dots (QDs) or metallic nanoparticles. Because they can exhibit several features synergistically and deliver more than one function simultaneously, such multifunctional magnetic nanoparticles could have unique advantages in biomedical applications. In this Account, we review examples of the design and biomedical application of multifunctional magnetic nanoparticles. After their conjugation with proper ligands, antibodies, or proteins, the biofunctional magnetic nanoparticles exhibit highly selective binding. These results indicate that such nanoparticles could be applied to biological medical problems such as protein purification, bacterial detection, and toxin decorporation. The hybrid nanostructures, which combine magnetic nanoparticles with other nanocomponents, exhibit paramagnetism alongside features such as fluorescence or enhanced optical contrast. Such structures could provide a platform for enhanced medical imaging and controlled drug delivery. We expect that the combination of unique structural characteristics and integrated functions of multicomponent magnetic nanoparticles will attract increasing research interest and could lead to new opportunities in nanomedicine.
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              Synthetic protein scaffolds provide modular control over metabolic flux.

              Engineered metabolic pathways constructed from enzymes heterologous to the production host often suffer from flux imbalances, as they typically lack the regulatory mechanisms characteristic of natural metabolism. In an attempt to increase the effective concentration of each component of a pathway of interest, we built synthetic protein scaffolds that spatially recruit metabolic enzymes in a designable manner. Scaffolds bearing interaction domains from metazoan signaling proteins specifically accrue pathway enzymes tagged with their cognate peptide ligands. The natural modularity of these domains enabled us to optimize the stoichiometry of three mevalonate biosynthetic enzymes recruited to a synthetic complex and thereby achieve 77-fold improvement in product titer with low enzyme expression and reduced metabolic load. One of the same scaffolds was used to triple the yield of glucaric acid, despite high titers (0.5 g/l) without the synthetic complex. These strategies should prove generalizeable to other metabolic pathways and programmable for fine-tuning pathway flux.
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                Author and article information

                Contributors
                zoher.gueroui@ens.fr
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                12 September 2017
                12 September 2017
                2017
                : 7
                : 11344
                Affiliations
                [1 ]École Normale Supérieure, PSL Research University, CNRS, UPMC, Department of Chemistry, 24 rue Lhomond, 75005 Paris, France
                [2 ]ISNI 0000 0004 0644 8455, GRID grid.462475.6, IMPMC. Sorbonne Université. CNRS. UPMC. MNHN. IRD. 4, ; place Jussieu, 75005 Paris, France
                Article
                10297
                10.1038/s41598-017-10297-y
                5595911
                28900114
                a8de3223-3197-4215-a377-57200e815b97
                © The Author(s) 2017

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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                : 2 May 2017
                : 7 August 2017
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