Insertion of γ-secretase into model membranes induces the redistribution of microdomains. (a−d) Time course (t = 147, 164, 191, and 283 min at 25 °C after loading) of reconstitution of γ-secretase into preformed DOPC/sphingomyelin/cholesterol (2:2:1)-supported bilayers on a glass-supported mica sheet. (e, f) 3D images zoomed into the rectangular ROIs in the previous two images (scale bar 100 nm). (g, h) Normalized local Lo domain changes over the course of the incubation, comparing enzyme-free areas (red; n = 3 ROIs) versus areas adjacent to high-density enzyme areas (blue; n = 4 ROIs).