Phase separation in hybrid polymer/lipid giant unillamelar vesicles (GHUVs) has been described over the last few years. However there is still a lack of understanding in physical and molecular factors governing the phase separation in such systems. Among these parameters it has been suggested that in analogy to multicomponent lipid vesicles that hydrophobic mismatchs as well as lipid fludity play a role.In this work, we aim to map a global picture of phase separation and domain formation in membrane of GHUVs by using various copolymers based on poly(dimethylsiloxane) (PDMS) and poly(ethylene glycol) (PEO) with different architectures (grafted, triblock) and molar masses, combined with lipid at fluid (POPC) or gel state (DPPC) at room temperature. From confocal imaging and fluorescence lifetime imaging microscopy technique (FLIM), the phase separation into either micro- or nano- domains within GHVs were studied. In particular, our systematic studies demonstrate that in addition to lipid/polymer fraction or lipid physical state, important factors such as line tension at lipid polymer/lipid boundaries can be finely modulated by the molar mass and architecture of the copolymer and lead to the formation of stable lipid domains with different sizes and morphologies in such GHUVs.< Leer menos