A Protein-Eye View of the In Meso Crystallization Mechanism

For evolving biological and biomedical applications of hybrid protein–lipid materials understanding the behavior of the protein within the lipid mesophase is crucial. After more than two decades since the invention of the in meso crystallization method, a protein-eye-view of its mechanism is still lacking. Numerous structural studies have suggested that integral membrane proteins preferentially partition at localized flat points on the bilayer surface of the cubic phase with crystal growth occurring from a local fluid lamellar Lα phase conduit. However, studies to date have, by necessity, focused on structural transitions occurring in the lipid mesophase. Here we demonstrate using small-angle neutron scattering (SANS) that the lipid bilayer of monoolein (the most commonly used lipid for in meso crystallization) can be contrast-matched using deuteration, allowing us to isolate scattering from encapsulated peptides during the crystal growth process for the first time. During in meso crystallization a clear ...