Effect of Lipid Headgroup Charge and pH on the Stability and Membrane Insertion Potential of Calcium Condensed Gene Complexes
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Issue Date
2015-04-14Author
Alhakamy, Nabil A.
Elandaloussi, Ibrahim
Ghazvini, Saba
Berkland, Cory J.
Dhar, Prajnaparamita
Publisher
American Chemical Society
Type
Article
Article Version
Scholarly/refereed, author accepted manuscript
Rights
@American Chemical Society
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Show full item recordAbstract
Noncovalently condensed complexes of genetic material, cell penetrating peptides (CPPs), and calcium chloride present a nonviral route to improve transfection efficiency of nucleic acids (e.g., pDNA and siRNA). However, the exact mechanisms of membrane insertion and delivery of macromolecule complexes to intracellular locations as well as their stability in the intracellular environment are not understood. We show that calcium condensed gene complexes containing different hydrophilic (i.e., dTAT, K9, R9, and RH9) and amphiphilic (i.e., RA9, RL9, and RW9) CPPs formed stable cationic complexes of hydrodynamic radii 100 nm at neutral pH. However, increasing the acidity caused the complexes to become neutral or anionic and increase in size. Using zwitterionic and anionic phospholipid monolayers as models that mimic the membrane composition of the outer leaflet of cell membranes and intracellular vesicles and pHs that mimic the intracellular environment, we study the membrane insertion potential of these seven gene complexes (CPP/pDNA/Ca2+ complexes) into model membranes. At neutral pH, all gene complexes demonstrated the highest insertion potential into anionic phospholipid membranes, with complexes containing amphiphilic peptides showing the maximum insertion. However, at acidic pH, the gene complexes demonstrated maximum monolayer insertion into zwitterionic lipids, irrespective of the chemical composition of the CPP in the complexes. Our results suggest -
Description
This document is the Accepted Manuscript version of a Published Work that appeared in final form in Langmuir, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://doi.org/10.1021/la504970n.
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Citation
Alhakamy, N. A., Elandaloussi, I., Ghazvini, S., Berkland, C. J., & Dhar, P. (2015). Effect of Lipid Headgroup Charge and pH on the Stability and Membrane Insertion Potential of Calcium Condensed Gene Complexes. Langmuir : The ACS Journal of Surfaces and Colloids, 31(14), 4232–4245. http://doi.org/10.1021/la504970n
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