The effect of lipid saturation on the formation of styrene maleic acid lipid nanoparticles

Abstract

The ability to use styrene maleic acid (SMA) to solubilize membrane proteins has been of significant interest. The formation of the lipid nanodiscs and extraction of the proteins without the use of detergent allows for the study of these membrane proteins in a more native environment. Traditional mimetic systems, such as micelles, bicelles, and liposomes all have compatibility limitations in their ability to provide a native environment for the protein. Lipid composition plays a significant role in the compatibility of these mimetic systems with membrane proteins. In this study, lipids with varying degrees of saturation are used to assess the efficacy of the SMA polymer in forming styrene maleic acid lipid nanoparticles (SMALPs). Lipids ranging from fully saturated to fully unsaturated are used along with two SMA polymers with various hydrophobic tail lengths. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) are used to characterize the liposomes and SMALPs. Continuous Wave-Electron Paramagnetic Resonance Spectroscopy (CW-EPR) is used to understand the effect of SMA on a spin-labeled membrane protein incorporated in the SMALP system. Results show the dynamic properties of membrane proteins incorporated in SMALPs are dependent on SMA polymer tail length as well as the lipid saturation. Lineshape analysis shows evidence of the hydrophobic tail of the SMA playing a role in how the protein is positioned within the SMALPs.