Figure 5.

Cellular mechanism of nonproteolytic movement within 3D collagen matrix and related changes in β1 integrin, MT1-MMP, and F-actin distribution in HT-1080/MT1 cells. (A) Induced amoeboid migration lacking fiber degradation. Alignment of cell body along a fiber strand (white arrowheads) and intact individual collagen fiber at its original position after cell detachment (black arrowhead). (B) Migratory alignment of the cell depicted in A along the preexisting fiber scaffold. The outline of the cell edge at 2.5-min time intervals (blue lines) was superimposed onto the 3D reconstruction of the transmigrated matrix structure. Bright pixels indicate colocalization of cell boundary and fibers (arrowheads). (C) Migration through a narrow gap bordered by fibers (black arrowhead) resulting in morphological adaptation and the formation of a constriction ring. (D) Reduced F-actin and β1 integrin focalization at fiber binding sites in an amoeboid HT1080/MT1 cell, compared with F and Fig. 1 C. Because of constriction caused by a perpendicular collagen fiber, this cell contains a lobulated main body. Black arrowhead, uropod. (E) Loss of clustered MT1-MMP and β1 integrins from interactions with fibers in induced amoeboid migration. Arrowheads indicate two simultaneous constriction rings bordered by perpendicular collagen fibers. (F) F-actin and β1 integrins in an untreated control cell of elongated shape. Time: (A) 35 min; (B) 65 min; (C) 20 min. Bars, 20 μm. Black arrows, direction of migration.