DIGITAL VISION
Michael Abercrombie was a pioneer in the study of cell behaviour. By setting up some of the first time-lapse experiments with chicken fibroblasts and a phase-contrast microscope, he described the cell-motility cycle, which is the basis of our current understanding of how cells migrate.
In 1953, Abercrombie and Heaysman first described how contact with neighbouring cells negatively regulates cell progression. The ability of cells to restrain each other's movement was defined as 'contact inhibition', and its implications for processes such as the organization of tissues during development, wound healing and the formation of metastasis were outlined.
In the 1970s, Abercrombie, Heaysman and Pegrum published five seminal papers that led to several hypotheses on the mechanisms of cell migration. The authors described how repeated cycles of membrane protrusion and withdrawal took place at the leading edge of the advancing cell. These motile sheet-like projections were defined as lamellipodia. Further analyses revealed that the rates of protrusion and withdrawal were similar, and that forward movement resulted from the greater proportion of time that a cell spent protruding. Membrane ruffles, which were visualized by phase- contrast microscopy as dark waves arising at the leading edge of the cells, were found to form mainly during the switch from protrusion to withdrawal, and to move centripetally towards the cell body. In addition, the retrograde movement of particles on the dorsal surface of the lamellipodia was noted. Together, these findings led to the idea that cell movement requires the rapid insertion of new material at the leading edge, which causes the excess surface to move backwards steadily.
...Although this paper was published more than half a century ago, it discusses contact inhibition, which is very important in the field of not only cell biology, but also pathology.
Yoshimi Takai
Detailed examination of lamellipodia by electron microscopy revealed the presence of discrete accumulations of dense material, which constitute sites of attachment to the substratum, and longitudinal filaments (see Milestone 12). This first glimpse into the cytoarchitecture of the leading edge raised the idea that adhesion to the substratum provided a means of traction, which together with contractile fibrils allowed a cell to pull itself forward. Indeed, subsequent studies have shown that both the continuous addition of membrane at the leading edge and the generation of tractional force at sites of adhesion enable cell movement. Furthermore, a key role for microtubules in the stabilization of the leading edge and the generation of directed motility has also emerged (see Further reading).
Despite powerful imaging, genetic and computational methods, many questions regarding the molecular mechanisms that underlie cell migration remain unanswered. In particular, the mechanisms of adhesion assembly and disassembly and the precise regulation of the cytoskeleton during cell motility are still subject of intense investigation.
