Modified LDLs induce and bind to membrane ruffles on macrophages

Macrophage foam cell formation in vitro requires uptake of modified low den sity lipoproteins (LDL) such as acetylated LDL (AcLDL) and moderately oxidi zed LDL (OxLDL), or beta-migrating very low density lipoprotein (beta VLDL) , a naturally occurring lipoprotein. Incubation of macrophages with AcLDL a nd OxLDL resulted in stimulation of membrane ruffle formation, while beta V LDL primarily resulted in increased numbers of microvilli. Time-lapse Alien video enhanced contrast differential interference contrast (AVEC-DIC) ligh t microscopy and correlative whole mount intermediate-voltage transmission electron microscopy (IVEM) was used to examine the dynamics of AcLDL stimul ated membrane ruffling and membrane ruffle ultrastructure. Stereo 3D surfac e replicas confirmed that AcLDL bound to these AcLDL-induced membrane ruffl es. Quantification of the plasma membrane surface area after incubation wit h AcLDL, beta VLDL or LDL confirmed that AcLDL stimulated membrane ruffling , while beta VLDL and LDL stimulated microvilli formation. These studies su ggest that modified LDLs induce circular membrane ruffles and modified LDLs bind to these ligand-induced membrane ruffles. (C) 1999 Wiley-Liss, Inc.