دورية أكاديمية
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: | Vasiliu T; Center of Advanced Research in Bionanoconjugates and Biopolymers, 'Petru Poni' Institute of Macromolecular Chemistry, Iasi 700487, Romania. aatto@mmk.su.se., Craciun BF; Center of Advanced Research in Bionanoconjugates and Biopolymers, 'Petru Poni' Institute of Macromolecular Chemistry, Iasi 700487, Romania. aatto@mmk.su.se., Neamtu A; Bioinformatics Laboratory, TRANSCEND IRO, Iaşi 700843, Romania., Clima L; Center of Advanced Research in Bionanoconjugates and Biopolymers, 'Petru Poni' Institute of Macromolecular Chemistry, Iasi 700487, Romania. aatto@mmk.su.se., Isac DL; Center of Advanced Research in Bionanoconjugates and Biopolymers, 'Petru Poni' Institute of Macromolecular Chemistry, Iasi 700487, Romania. aatto@mmk.su.se., Maier SS; Center of Advanced Research in Bionanoconjugates and Biopolymers, 'Petru Poni' Institute of Macromolecular Chemistry, Iasi 700487, Romania. aatto@mmk.su.se.; Polymers Research Center, 'Gheorghe Asachi' Technical University of Iasi, Iasi, 700487, Romania., Pinteala M; Center of Advanced Research in Bionanoconjugates and Biopolymers, 'Petru Poni' Institute of Macromolecular Chemistry, Iasi 700487, Romania. aatto@mmk.su.se., Mocci F; Center of Advanced Research in Bionanoconjugates and Biopolymers, 'Petru Poni' Institute of Macromolecular Chemistry, Iasi 700487, Romania. aatto@mmk.su.se.; Dipartimento di Scienze Chimiche e Geologiche, Università di Cagliari, Monserrato, 09042 Cagliari, Italy., Laaksonen A; Center of Advanced Research in Bionanoconjugates and Biopolymers, 'Petru Poni' Institute of Macromolecular Chemistry, Iasi 700487, Romania. aatto@mmk.su.se.; Department of Materials and Environmental Chemistry, Division of Physical Chemistry, Arrhenius Laboratory, Stockholm University, 106 91 Stockholm, Sweden.; State Key Laboratory of Materials-Oriented and Chemical Engineering, Nanjing Tech University, 210009 Nanjing, PR China.; Department of Engineering Sciences and Mathematics, Division of Energy Science, Luleå University of Technology, 97187 Luleå, Sweden. |
| المصدر: | Biomaterials science [Biomater Sci] 2021 Sep 28; Vol. 9 (19), pp. 6623-6640. Date of Electronic Publication: 2021 Sep 28. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Royal Society of Chemistry Country of Publication: England NLM ID: 101593571 Publication Model: Electronic Cited Medium: Internet ISSN: 2047-4849 (Electronic) Linking ISSN: 20474830 NLM ISO Abbreviation: Biomater Sci Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Cambridge, UK : Royal Society of Chemistry |
| مواضيع طبية MeSH: | Polyethylene Glycols* , Squalene*, Computer Simulation ; DNA ; Particle Size ; Polyethyleneimine ; Transfection |
| مستخلص: | 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. |
| المشرفين على المادة: | 3WJQ0SDW1A (Polyethylene Glycols) 7QWM220FJH (Squalene) 9002-98-6 (Polyethyleneimine) 9007-49-2 (DNA) |
| تواريخ الأحداث: | Date Created: 20210928 Date Completed: 20210930 Latest Revision: 20210930 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1039/d1bm00973g |
| PMID: | 34582532 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2047-4849 |
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| DOI: | 10.1039/d1bm00973g |