Nanodiamonds as "artificial proteins": Regulation of a cell signalling system using low nanomolar solutions of inorganic nanocrystals
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
29879652
DOI
10.1016/j.biomaterials.2018.05.030
PII: S0142-9612(18)30373-9
Knihovny.cz E-zdroje
- Klíčová slova
- Cell signalling, FGF, Fibroblast growth factor, Nanodiamonds, Nanotherapeutics,
- MeSH
- aminokyselinové motivy MeSH
- buněčné linie MeSH
- chrupavka fyziologie MeSH
- embryo savčí MeSH
- fibroblastové růstové faktory metabolismus MeSH
- lidé MeSH
- ligandy MeSH
- myši MeSH
- nanodiamanty chemie MeSH
- proliferace buněk MeSH
- receptory fibroblastových růstových faktorů metabolismus MeSH
- signální transdukce MeSH
- techniky tkáňových kultur MeSH
- tibie fyziologie MeSH
- vazba proteinů MeSH
- viabilita buněk MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- fibroblastové růstové faktory MeSH
- ligandy MeSH
- nanodiamanty MeSH
- receptory fibroblastových růstových faktorů MeSH
The blocking of specific protein-protein interactions using nanoparticles is an emerging alternative to small molecule-based therapeutic interventions. However, the nanoparticles designed as "artificial proteins" generally require modification of their surface with (bio)organic molecules and/or polymers to ensure their selectivity and specificity of action. Here, we show that nanosized diamond crystals (nanodiamonds, NDs) without any synthetically installed (bio)organic interface enable the specific and efficient targeting of the family of extracellular signalling molecules known as fibroblast growth factors (FGFs). We found that low nanomolar solutions of detonation NDs with positive ζ-potential strongly associate with multiple FGF ligands present at sub-nanomolar concentrations and effectively neutralize the effects of FGF signalling in cells without interfering with other growth factor systems and serum proteins unrelated to FGFs. We identified an evolutionarily conserved FGF recognition motif, ∼17 amino acids long, that contributes to the selectivity of the ND-FGF interaction. In addition, we inserted this motif into a de novo constructed chimeric protein, which significantly improved its interaction with NDs. We demonstrated that the interaction of NDs, as purely inorganic nanoparticles, with proteins can mitigate pathological FGF signalling and promote the restoration of cartilage growth in a mouse limb explant model. Based on our observations, we foresee that NDs may potentially be applied as nanotherapeutics to neutralize disease-related activities of FGFs in vivo.
Central European Institute of Technology Masaryk University 62500 Brno Czech Republic
Department of Biology Faculty of Medicine Masaryk University 62500 Brno Czech Republic
Division of Neuroanatomy Medical University of Innsbruck A 6020 Innsbruck Austria
EMAT University of Antwerp Groenenborgerlaan 171 B 2020 Antwerp Belgium
Institute of Experimental Biology Faculty of Sciences Masaryk University 62500 Brno Czech Republic
Institute of Neuroanatomy and Cell Biology Hannover Medical School 30625 Hannover Germany
Institute of Organic Chemistry and Biochemistry of the CAS 16610 Prague Czech Republic
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