Four hybrid double-chain surfactants with a maltose polar head were synthesized. The apolar domain consists of a hydrogenated chain, and a partially fluorinated chain made of a propyl hydrogenated spacer terminated by a perfluorinated core of various lengths. Their water solubility was found to be lower than 1 g/L irrespective of the length of both chains. The self-assembling properties of pure hybrids in water were studied by dynamic light scattering and transmission electron microscopy, which revealed the formation of two populations of aggregates with diameters of 8–50 nm and 80–300 nm. When mixed with the classical detergent n-dodecylmaltoside (DDM), the four hybrids were well soluble and formed small mixed micelles. DDM/hybrid mixtures were further evaluated for the extraction of the full-length, wild-type human GPCR adenosine receptor (A2AR), and the bacterial transporter AcrB. The solubilization of A2AR showed extraction efficiencies ranging from 40 to 70%, while that of AcrB reached 60–90%. Finally, three of the hybrids exhibited significant thermostabilization when present as additives. The derivative with a C12-hydrogenated chain and a C4F9-fluorinated chain emerged as the most potent additive exhibiting both good extraction yields of A2AR and AcrB and thermostabilization of A2AR by ∼7 °C.

Three monomers with a maltose polar head, an alkyl hydrogenated chain, and an acrylamide‐based polymerizable moiety were synthesized. The self‐assembly properties in aqueous solutions of these monomers were studied by means of isothermal titration calorimetry (ITC), surface tension (SFT) measurements, and dynamic light scattering (DLS), which indicated the formation of small micellar aggregates of about 6 nm diameter. The critical micellar concentration (CMC) was found to depend on the length of the alkyl chain and on the nature of the polymerizable moiety, ranging from 0.35 mm to ca. 10 mm. The monomers were found to solubilize phospholipid vesicles and to extract a broad range of proteins from Escherichia coli membranes. Finally, the extraction of two membrane proteins, namely, the full‐length, wild‐type human G‐protein‐coupled receptor (GPCR) adenosine A2A receptor (A2AR) and the bacterial transporter AcrB was demonstrated.