Surfmer versus Polymer Effect toward Solubilization and Stabilization of Membrane Proteins

We have synthesized four acrylamide-based monomers whose polar headgroup consists of one or two glucose or one maltose moieties and whose alkyl chain is made of a n-decyl or a n-octyl hydrophobic chain. These surface-active monomers, called surfmers, were polymerized by free-radical telomerization in the presence of a thiol-based transfer agent, leading to four new nonionic polymers that belong to the class of amphipols. A very good reproducibility and control of the polymerization was noted, leading to average polymerization degrees in perfect agreement with the initial ratio R (0) and to quite a narrow polydispersity index after purification. Surface tension (SFT) measurements indicate that the four surfmers self-assemble at concentrations ranging from similar to 0.5 to 4 mM. Dynamic light scattering (DLS) experiments suggest the formation of rather small homogeneous aggregates of 5 nm diameter for the monomers, while the size of the aggregates ranges from 5 to 16 nm diameter for the polymers. The ghrelin receptor GHSR, a typical rhodopsin-like G protein-coupled receptor (GPCR), was used as a challenging model because of its conformational instability in vitro. The surfmers solubilized the receptor from membrane fractions more efficiently than their polymeric counterparts. In contrast, the polymers were significantly more efficient at stabilizing the functional fold of the isolated protein in solution. This demonstrates the opposite effect of surfmers and their polymer counterparts toward the solubilization and stabilization of a fragile membrane protein.