BHEM-Chol/DOPE liposome induced perturbation of phospholipid bilayer

Abstract

A new positively charged cholesteryl lipid known as BHEM-Chol is developed as a membrane perturbant. It has been shown that this cationic liposome effectively fuses with cell membrane. In this study, the interaction between BHEM-Chol/DOPE liposome and dipalmitoylphosphocholine (DPPC) bilayer is investigated with cross-polarization microscopy, differential scanning calorimetry (DSC) and cooperative unit analysis in order to aid the physical understanding in the cationic liposome–biological membrane interaction. The presence of BHEM-Chol/DOPE liposome in DPPC/water mixture leads to the formation of larger multilamellar vesicles (MLV) and also induces fusions of pre-assembled MLV. The pre-transition peak of DPPC bilayer is abolished under the influence BHEM-Chol/DOPE liposome. When the mole fraction of BHEM-Chol/DOPE liposome is increased from 0 to 0.7, the calorimetric enthalpy of DPPC bilayer is reduced by 63%. Simultaneously, the phase transition temperature of DPPC bilayer is shifted to lower value and is accompanied by the reduction of cooperative unit. The thermotropic property of DPPC bilayer during sample cooling is also affected by this new liposome system. In addition, the interaction between DPPC bilayer and a commercial DC-Chol/DOPE liposome is used as a reference. Most important, BHEM-Chol provides the major driving force for membrane perturbation as shown by the 38% reduction in calorimetric enthalpy in aqueous DPPC/BHEM-Chol mixture. Cell culture media further modulates the structural properties of the aqueous mixture. In addition, in vitro transfection studies of COS-7 cells mediated by both BHEM-Chol/DOPE and DC-Chol/DOPE liposomes are presented and provide a qualitative correlation with our biophysical measurements.