Use of detergents to study membrane rafts: The good, the bad, and the ugly

Eukaryotic cell membranes contain microdomains called lipid rafts, which are cholesterolrich domains in which lipid acyl chains are tightly packed and highly extended. A variety of proteins associate preferentially with rafts, and this raft association is important in a wide range of functions. A powerful and widely used method for studying lipid rafts takes advantage of their insolubility in nonionic detergents. Here we describe the basis of detergent insolubility, and review strengths, limitations, and unresolved puzzles regarding this method.