While conventional negative stain electron microscopy (NSEM) has been used extensively for imaging and characterizing high density lipoprotein (HDL) particles, traditional methods have not provided high-level particle surface detail. To obtain greater detail of HDL particles, we developed a modified negative staining procedure using a uranyl formate staining solution that maintains particle morphology and provides improved surface detail. The additional surface detail has allowed us to perform single-particle analysis on whole HDL particle preparations. It has also allowed us to explore interactions between HDL particle surface proteins such as Apo A with proteins that interact with Apo A such as lecithin-cholesterol acyltransferase (LCAT).
