Research in the Lorieau group integrates Biophysics, Physical Chemistry, Structural Biology and Biochemistry in elucidating the interplay between biomolecular structure, dynamics, chemistry and function. With a combination of solution- and solid-state Nuclear Magnetic Resonance spectroscopies, computational tools and other biophysical methods, our research focuses on membrane protein structure and dynamics, membrane protein biochemistry, the development of theory and techniques to enhance the precision and resolution of structural and dynamic information by NMR, and the investigation of molecular dynamics as it relates to enzymatic catalysis and kinetics.
- Membrane protein and membrane channel structure, dynamics and function
- Methods for the high-resolution characterization of structure and dynamics for solution-state and solid-state nuclear magnetic resonace of large molecular-weight biomolecules
- Software development for the simulation of magnetic resonance, including data and statistical analysis of multidimensional datasets
Isotropically tumbling discoidal bicelles are a useful biophysical tool for the study of lipids and proteins by NMR, dynamic light scattering, and small-angle X-ray scattering. Isotropically tumbling bicelles present a low-curvature central region, typically enriched with DMPC in the lamellar state, and a highly curved detergent rim, typically composed of DHPC. In this report, we study the impact of the partitioning and induced curvature of a few molecules of a foreign lipid on the bicelle size, structure, and curvature. Previous approaches for studying curvature have focused on macroscopic and bulk properties of membrane curvature. In the approach presented here, we show that the conical shape of the DOPE lipid and the inverted-conical shape of the DPC lipid induce measurable curvature changes in the bicelle size. Bicelles with an average of 1.8 molecules of DOPE have marked increases in the size of bicelles, consistent with negative membrane curvature in the central region of the bicelle. With bicelle curvature models, radii of curvature on the order of −100 Å and below are measured, with a greater degree of curvature observed in the more pliable Lα state above the phase-transition temperature of DMPC. Bicelles with an average of 1.8 molecules of DPC are reduced in size, consistent with positive membrane curvature in the rim, and at higher temperatures, DPC is distributed in the central region to form mixed-micelle structures. We use translational and rotational diffusion measurements by NMR, size-exclusion chromatography, and structural models to quantitate changes in bicelle size, curvature, and lipid dynamics.