TEM analysis of collagen phagocytosis. Representative images showing the internalization of collagen fibrils by HGFs grown for 72 h in the presence of 10 μM E-64d on reconstituted collagen (A) and calvarial collagen (B). At sites of collagen fibril engulfment (white arrows) the cell membrane often appears electron dense (white arrowheads). (C and D) Compared with untreated cells (A and B), cells stimulated with ConA show increased degradation of the underlying reconstituted collagen beneath a scalloped cell surface (white arrows), the membranes of which were frequently more electron dense (white arrowheads). An increase in phagosomes and phagolysosomes (black arrows) and mitochondria (M) is also seen in the ConA-treated cells. (E and F) ConA-treated cells grown on rat-tail collagen. The banding pattern of the collagen in the thicker fibrils is more readily seen. In E, a cell process (black arrow) seems to be wrapped around a fibril before fragmentation, whereas in F, a similar fibril seems to be undergoing fragmentation within a forming vacuole, as indicated by the loss of the fibril structure (white arrows). Bars, 500 nm.