Determining the effects of PEI adsorption on the permeability of 1,2-dipalmitoylphosphatidylcholine/bis(monoacylglycero)phosphate membranes under osmotic stress

Polycations are used for a number of biological applications, including antibiotics and gene therapy. One aspect of the use of polycation gene carriers such as polyethylenemine (PEI) in gene therapy that is not well understood is their ability to escape from the vesicles they are internalized in. Here, in an attempt to gain a better understanding of PEI interaction with endosomal lipids under osmotic stress, we performed investigations using monolayers and vesicles derived from a mixture of neutral and negative lipids (1,2-dipalmitoylphosphatidylcholine (DPPC) and bis(monoacylglycero)phosphate (BMP), respectively). X-ray reflectivity (XR) and Langmuir trough measurements confirmed PEI adsorption to the negatively charged membrane. Confocal microscopy imaging indicated that PEI adsorption actually increases the overall integrity of the DPPC/BMP vesicle against osmotic stresses while also causing overall deformation and permeabilization of the lipid membrane, thus leading to leakage of contents from the interior of the vesicle. These confocal microscopy observations were also supported by data gathered by dynamic light scattering (DLS)


Scott R. Clark1,2,3, Keel Yong Lee4,5, Hoyoung Lee1, Jawahar Khetan1, Hyun Chang Kim1, Yun Hwa Choi1, Kwanwoo Shin4, You-Yeon Won1,6,7

1School of Chemical Engineering, Purdue University, West Lafayette, IN 47907, USA

2West Lafayette Junior/Senior High School, West Lafayette, IN 47906, USA

3Department of Chemistry, Purdue University, West Lafayette, IN 47907, USA

4Department of Chemistry, and Institute of Biological Interfaces, Sogang University, Seoul 04107, Republic of Korea

5Department of Energy Science, Sungkyunkwan University, Suwon 16419, Republic of Korea

6Purdue University Center for Cancer Research, Purdue University, West Lafayette, IN 47907, USA

7Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science & Technology, Seoul 02792, Republic of Kore

Acta Biomaterialia, 2018, 65, pp 317-326

DOI: 10.1016/j.actbio.2017.10.027