(A) Histology image of a human nephrectomized kidney biopsy. (B) Glomerulus image showing normal pathology. (C) Slice through a cryo-electron tomogram of the filtration system. Foot processes (fp; yellow) contain actin filaments. The top view (en face) of the SD shows crisscrossing strands forming a fishnet; strands spanning the membrane indicated by blue and pink arrows. (D) Isosurface representation of the cryo-electron tomogram (in C) displaying the SD (in blue) from the top view spanning the 2 plasma membranes (in beige) of the fp. Large areas of the fp are filled with branched actin (in green). (E) Three orthogonal views — membrane view (blue frame), classical view (orange frame), and top view (green frame) — of computational sections through the sub-tomogram average. Crisscrossing densities span the plasma membranes (“mem”) of fp. Membrane and classical views show individual strand sections (dots), and top and isosurface views reveal a fishnet pattern with the strands crossing at ~90°. The isosurface view of the sub-tomogram average shows the fishnet pattern with internal structural holes. Diagonal light blue and pink lines indicate crossing strands, highlighting the fishnet pattern. Lines are spaced 9 nm apart. (F) Idealized molecular model of the human SD shown in 2 orthogonal views. The Nephrin-Neph1 heterodimer was used as a unit cell and placed in 1-dimensional crystal packing. One heterodimer is highlighted in gold with the putative interfaces shown in various colors. All other heterodimers are shown in gray (Nephrin in light gray and Neph1 in dark gray). Each heterodimer is predicted to interact with 6 other heterodimers.