Antenna-Based Optical Imaging of Single Ca2+ Transmembrane Proteins in Liquids

Understanding the diversity of biological processes requires methods that can address single proteins in their natural environment and provide insights into structural and functional properties, as well as the local distribution of each individual protein. We use an optical antenna in the form of a single gold nanoparticle to localize incident laser radiation to 50 nm, significantly smaller than the diffraction limit of light. Our approach enables us to optically resolve individual plasma-membrane-bound Ca2+ pumps (PMCA4) immersed in aqueous environments and to determine the distribution of interprotein distances. We are able to correlate the protein maps with local topology. Improved antenna geometries will make it possible to resolve, identify, and probe single membrane proteins in live cells with true protein resolution of 5−10 nm.