Nature of the Charged Headgroup Determines the Fusogenic Potential and Membrane Properties of Lithocholic Acid Phospholipids

Phospholipids play a crucial role in many cellular processes ranging from selective membrane permeability, to membrane fission and fusion, to cellular signaling. Headgroups of phospholipids determine the membrane properties and fusogenicity of these lipids with target cell membranes. We studied the fusogenic and membrane properties of phospholipids possessing unnatural charged headgroups with model membranes using laurdan based membrane hydration studies, DPH based membrane fluidity, and differential scanning calorimetry. We unravel that fusogenicity, membrane hydration, and fluidity of membranes are strongly contingent on the nature of the phospholipid charged headgroup. Our studies unraveled that introduction of bulky headgroups like dimethylamino pyridine induces maximum membrane hydration and perturbations with high fusogenicity as compared to small headgroup based phospholipids. These phospholipids also have the capability of high retention in DPPC membranes. Hydration and fluidity of these phospholipid-doped DPPC membranes are contingent on the nature of the charged headgroup. This study would help in future design of phospholipid based nanomaterials for effective drug delivery.