Mechanism of the interaction of hydrophobically-modified poly-(N-isopropylacrylamides) with liposomes

Abstract

Interactions of hydrophobically-modified poly-(N-isopropylacrylamides) (HM PNIPAM) with phospholipid liposomes were studied as a function of the lipid type, the lipid bilayer fluidity, and the polymer conformation. Fluorescence experiments monitoring non-radiative energy transfer (NRET), between naphthalene attached to the HM PNIPAM and 1,6-diphenyl-1,3,5-hexatriene (DPH) incorporated into the lipid bilayer, confirmed the direct penetration of hydrophobic anchor groups linked to the polymer into the liposome hydrophobic core. Contraction of the polymer backbone above the lower critical solution temperature (LCST) resulted in a partial withdrawal of the anchor groups from the lipid bilayer. Analysis of polymer/lipid mixtures by centrifugation and quasi-elastic light scattering (QELS) revealed the polymer-induced fission of liposomes in the liquid-crystalline state, resulting in the formation of vesicles 150-230 nm in diameter. The process is reversible and upon transition of the bilayer into the gel state these vesicles are converted into larger aggregates. According to the results of gel-filtration experiments the HM PNIPAM is in dynamic exchange between the liquid-crystalline lipid bilayer and the water solution, while the binding to the bilayer in the gel state is more static in nature. The binding constant for mixture of HM PNIPAM with DMPC liposomes, evaluated from the centrifugation experiments, was found to be 120 M(-1).

Rheological study of hydrophobically modified hydroxyethyl cellulose and phospholipid vesicles

“…Accordingly, the DPPC bilayers are always in the gel state for all the rheology measurements in our study, whereas the EPC bilayers having a phase transition temperature from À15 to À5°C are in the fluid state. A previous study on HMPNIPAM with DMPC (T m % 23.5°C) and EPC [31] found that the bilayer fluidity appeared not to affect the polymer binding efficiency, while a more uniform distribution of hydrophobes was detected for liposomes in the fluid state. The hydrophobes were thought to exchange faster and more dynamically between water and bilayers in the fluid state than in the gel state.…”

“…Unlike surfactant vesicles, no phase separation was observed for phospholipid vesicles mixed with HMPs [25][26][27][28][29][30][31][32]. Phospholipid vesicles naturally mimic the biological cells, making them a better candidate in the study of fundamental interaction between cells and polymers [33][34][35][36].…”

“…The insertion of the hydrophobic anchor was evidenced by decreased pyrene excimer emission. Polozova et al [31] further studied this system, focusing on the effects of lipid type, phase state, and polymer conformation. Adsorption of hydrophobically modified polysaccharide to liposomes was studied by Sunamoto et al [27].…”

Membrane-Anchoring, Comb-Like Pseudopeptides for Efficient, pH-Mediated Membrane Destabilization and Intracellular Delivery

“…31 Other researchers have reported that even a small number of long alkyl side chains can facilitate the deeper insertion of poly(N-isopropylacrylamides) derivatives into the liposomal bilayer. 32 The ability of PLP-NDA 18% to hemolyze RBCs at endosomal pH 5.5 and physiological pH was further evaluated as a function of polymer concentration ( Figure 3B). PLP-NDA 18%…”

Slow Reorganization of Small Phosphatidylcholine Vesicles upon Adsorption of Amphiphilic Polymers

“…Like conventional detergents, macromolecules can however strongly modulate the permeability of the membrane (9)(10)(11)(12), modify the curvature energy (13), and solubilize lipids in mixed micelles (14). The enhancement of liposome fusions can also result from polymer adsorption as reported by Polozova and Winnick in the case of modified poly(N -isopropylacrylamide) (15), by Kono et al on the example of decyl-modified poly(glycidol)s (16), or by Hara et al on an amphiphilic polymer consisting of octadecylacrylamide and N,N-dimethylacrylamide (17). At variance with conventional detergent molecules, the structure of a polymer can be varied in a continuous manner, by changing gradually the charge density or the hydrophobicity of long chains, making it possible to tune the stability of vesicles.…”