Partitioning, diffusion, and ligand binding of raft lipid analogs in model and cellular plasma membranes

►Raft lipid analogs show mispartitioning in both synthetic and cell-derived membrane systems. ►The partitioning of an analog is a function of type, size, polarity, charge and position of the dye. ►Acyl-chain labeling directly modulates bioactivity of lipids in a phase-specific manner. ►Partitioning in cell-derived GPMVs more closely follows raft predictions than in synthetic GUVs. ►Nanoscale diffusion in live cell membranes is uncorrelated with partitioning in model membranes.