Composition of raft-like cell membrane microdomains resistant to styrene-maleic acid copolymer (SMA) solubilization

An advantageous alternative to the use of detergents in biochemical studies on membrane proteins have recently been styrene-maleic acid (SMA) amphipathic copolymers. These cut the membrane into nanodiscs (often called SMA-lipid particles, SMALPs), which contain membrane proteins surrounded by their relatively native lipid environment. In our recent study [1] we demonstrated that using this approach, most T cell membrane proteins were fully solubilized (presumably in small nanodiscs), while two types of raft proteins, GPI-anchored proteins and Src family kinases, were mostly present in much larger (>250 nm) membrane fragments markedly enriched in typical raft lipids, cholesterol and lipids containing saturated fatty acid residues. In the present study we demonstrate that disintegration of membranes of several other cell types by means of SMA copolymer follows a similar pattern and we provide a detailed proteomic and lipidomic characterization of these SMA-resistant membrane fragments (SRMs).