Steered molecular dynamics simulations reveal a self-protecting configuration of nanoparticles during membrane penetration
- PMID: 30206609
- DOI: 10.1039/c8nr04287j
Steered molecular dynamics simulations reveal a self-protecting configuration of nanoparticles during membrane penetration
Abstract
Cell entry of polynucleotide-based therapeutic agents can be facilitated by nanoparticle (NP) mediated delivery. In this work, using steered molecular dynamics simulations, we simulated the membrane penetration process of a NP formed by 2 short interfering RNA (siRNA) and 6 polyethylenimine (PEI) molecules. To the best of our knowledge, this is the first set of simulations that explore the direct penetration of an siRNA/PEI NP through a membrane at an all-atom scale. Three types of PEI molecules were used for NP formation: a native PEI, a PEI modified with caprylic acids and a PEI modified with linoleic acids. We found that hydrogen bond formation between the PEIs and the membrane did not lead to instability of the siRNA/PEI NPs during the internalization process. Instead, our results suggested adoption of a "self-protecting" configuration by the siRNA/PEI NP during membrane penetration, where the siRNA/PEI NP becomes more compact and siRNAs become aligned, leading to more stable configurations while detaching from the membrane. The siRNA/PEI NP modified with linoleic acid showed the smallest structural change due to its strong intra-particle lipid associations and the resulting rigidity, while NP modified with caprylic acid showed the largest structural changes. Our observations provide unique insight into the structural changes of siRNA/PEI NPs when crossing the cell membrane, which can be important for the design of new NP carriers for nucleic acid delivery.
Similar articles
-
Nature of bilayer lipids affects membranes deformation and pore resealing during nanoparticle penetration.Mater Sci Eng C Mater Biol Appl. 2022 Jan;132:112530. doi: 10.1016/j.msec.2021.112530. Epub 2021 Nov 12. Mater Sci Eng C Mater Biol Appl. 2022. PMID: 35148864
-
Membrane lipids destabilize short interfering ribonucleic acid (siRNA)/polyethylenimine nanoparticles.Nanoscale. 2020 Jan 2;12(2):1032-1045. doi: 10.1039/c9nr08128c. Nanoscale. 2020. PMID: 31845926
-
Polyethylenimines for siRNA and miRNA delivery in vivo.Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2013 Sep-Oct;5(5):484-501. doi: 10.1002/wnan.1228. Epub 2013 May 29. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2013. PMID: 23720168 Review.
-
A molecular dynamics simulation study on the effect of lipid substitution on polyethylenimine mediated siRNA complexation.Biomaterials. 2013 Apr;34(11):2822-33. doi: 10.1016/j.biomaterials.2013.01.011. Epub 2013 Jan 23. Biomaterials. 2013. PMID: 23352043
-
Polyethylenimines for RNAi-mediated gene targeting in vivo and siRNA delivery to the lung.Eur J Pharm Biopharm. 2011 Apr;77(3):438-49. doi: 10.1016/j.ejpb.2010.11.007. Epub 2010 Nov 18. Eur J Pharm Biopharm. 2011. PMID: 21093588 Review.
Cited by
-
Acidic Conditions Impact Hydrophobe Transfer across the Oil-Water Interface in Unusual Ways.J Phys Chem B. 2023 May 4;127(17):3911-3918. doi: 10.1021/acs.jpcb.3c00828. Epub 2023 Apr 21. J Phys Chem B. 2023. PMID: 37084419 Free PMC article.
-
Investigation of the ionic conditions in SiRNA-mediated delivery through its carriers in the cell membrane: a molecular dynamic simulation.Sci Rep. 2022 Oct 20;12(1):17520. doi: 10.1038/s41598-022-22509-1. Sci Rep. 2022. PMID: 36266467 Free PMC article.
-
The penetration of human defensin 5 (HD5) through bacterial outer membrane: simulation studies.J Mol Model. 2021 Sep 21;27(10):291. doi: 10.1007/s00894-021-04915-w. J Mol Model. 2021. PMID: 34546425
-
Metadynamics-Based Approaches for Modeling the Hypoxia-Inducible Factor 2α Ligand Binding Process.J Chem Theory Comput. 2021 Jul 13;17(7):3841-3851. doi: 10.1021/acs.jctc.1c00114. Epub 2021 Jun 3. J Chem Theory Comput. 2021. PMID: 34082524 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous