In silico study of PEI-PEG-squalene-dsDNA polyplex formation: the delicate role of the PEG length in the binding of PEI to DNA
العنوان: | In silico study of PEI-PEG-squalene-dsDNA polyplex formation: the delicate role of the PEG length in the binding of PEI to DNA |
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المؤلفون: | Dragos Lucian Isac, Tudor Vasiliu, Andrei Neamtu, Aatto Laaksonen, Stelian S. Maier, Bogdan Florin Craciun, Francesca Mocci, Mariana Pinteala, Lilia Clima |
المصدر: | Biomaterials Science. 9:6623-6640 |
بيانات النشر: | Royal Society of Chemistry (RSC), 2021. |
سنة النشر: | 2021 |
مصطلحات موضوعية: | Hydrogen bond, In silico, technology, industry, and agriculture, Biomedical Engineering, macromolecular substances, Polyethylene glycol, Transfection, Gene delivery, chemistry.chemical_compound, Electrophoresis, chemistry, PEG ratio, Biophysics, General Materials Science, DNA |
الوصف: | Biocompatible hydrophilic polyethylene glycol (PEG) is widely used in biomedical applications, such as drug or gene delivery, tissue engineering or as an antifouling component in biomedical devices. Experimental studies have shown that the size of PEG can weaken polycation-polyanion interactions, like those between branched polyethyleneimine (b-PEI) and DNA in gene carriers, but details of its cause and underlying interactions on the atomic scale are still not clear. To better understand the interaction mechanisms in the formation of polyplexes between b-PEI-PEG based carriers and DNA, we have used a combination of in silico tools and experiments on three multicomponent systems differing in PEG MW. Using the PEI-PEG-squalene-dsDNA systems of the same size, both in the all-atom MD simulations and in experimental in-gel electrophoresis measurements, we found that the binding between DNA and the vectors is highly influenced by the size of PEG, with the binding efficiency increasing with a shorter PEG length. The mechanism of how PEG interferes with the binding between PEI and DNA is explained using a two-step MD simulation protocol that showed that the DNA-vector interactions are influenced by the PEG length due to the hydrogen bond formation between PEI and PEG. Although computationally demanding we find it important to study molecular systems of the same size both in silico and in a laboratory and to simulate the behaviour of the carrier prior to the addition of bioactive molecules to understand the molecular mechanisms involved in the formation of the polyplex. |
تدمد: | 2047-4849 2047-4830 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::bc2f2123d9d1c277bc769ed3d2bfeac3 https://doi.org/10.1039/d1bm00973g |
حقوق: | OPEN |
رقم الأكسشن: | edsair.doi...........bc2f2123d9d1c277bc769ed3d2bfeac3 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 20474849 20474830 |
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