Dynamics and stability of lipid bilayers modulated by thermosensitive polypeptides, cholesterols, and PEGylated lipids
Journal
PCCP (Physical Chemistry Chemical Physics)
Date
2014.01.29
Abstract
Lipid bilayers, which consist of dipalmitoylglycerophosphocholines (DPPCs), PEGylated lipids, cholesterols, and elastin-like polypeptides (ELPs; [VPGVG]3) at different molar ratios, were simulated. Simulations were carried out for 2 ？s with the coarse-grained (CG) model that had captured the experimentally observed phase behavior of PEGylated lipids and lateral diffusivity of DPPC bilayers. Starting with the initial position of ELPs on the bilayer surface, ELPs insert into the hydrophobic region of the bilayer because of their interaction with lipid tails, consistent with previous all-atom simulations. Lateral diffusion coefficients of DPPCs significantly increase in the bilayer composed of more ELPs and less cholesterols, showing their opposite effects on the bilayer dynamics. In particular, ELPs modulate the dynamics and phase for the disordered liquid bilayer, but not for the ordered gel bilayer, indicating that ELPs can destabilize only the disordered bilayer. In the ordered bilayer, ELP chains tend to have a spherical shape and slowly diffuse, while they are extended and diffuse faster in the disordered bilayer, indicating the effect of the bilayer phase on the conformation and diffusivity of ELPs. These findings explain the experimental observation that showed that the ELP-conjugated liposome is stable at 310 K (ordered phase) but becomes unstable and release the encapsulated drugs at 315 K (disordered phase), which suggested the effects of ELPs and cholesterols. Since the cholesterol-stabilized bilayer can be destabilized by the extended shaped ELPs only in disordered phase (not in ordered phase), the inclusion of cholesterols is required to safely shield drugs at 310 K as well as allow ELPs to disrupt lipids and destabilize the liposome at 315 K.