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.