504
A . A . M O S C O N A
the cell surface which are removed or modified at dissociation; nonaggregation of differentiated cells could thus mean that such cells, in
being committed to, or engaged in, specialized biosynthetic activities,
are no longer able to regenerate their surface materials to their full
effectiveness; therefore, when removed from their native matrix, such
cells do not reconstitute the sort of surface that is essential for effective
mutual attachments. While these are undoubtedly oversimplified considerations, the phenomenon emphasizes clearly the dynamic nature of
cell contact and cell binding mechanisms, and particularly their correlation with functional or developmental states of the cells. It may be
appropriate to recall here that cells entering mitosis, and therefore
involved in specific metabolic tasks, round off, become temporarily
detached and show no contact inhibition (Abercrombie, 1958). It is
also of interest that changes in the biosynthetic patterns of cultured
cells due to infection with Rous virus are accompanied by decreased
adhesiveness (Rubin, 1961). In this connexion it should be stated that
decline in the ability to aggregate during development does not necessarily imply irreversible loss of cohesive competence: according to
Sigel, Scotti, Wryk and Dorsey (1959) cells from the kidney of the
adult monkey grown in monolayer for one passage produced nephric
aggregates when grafted to the brain.
The possibility of a significant relationship between the functional
state of cells and their adhesive properties is further suggested by
studies on cells which have been first grown as monolayers. Dissociated
embryonic cells grown in monolayer cultures were harvested periodically and tested by rotation for their capacity for aggregation; it was
found that this declined progressively, the change being most striking in
the first 2-4 days, then leveling off (embryonic retina, skin cells:
Moscona, 1960; cartilage cells: Kuroda, 1963). The rate of decline,
measured as decrease in size of aggregates, varied for the different types
of cells tested, and according to the age of the donor embryo, the conditions of culture, and the completeness of initial monolayering.
Kuroda (1963) studied aggregation by rotation of trypsin-dissociated
cells from the long bones of 13-day chick embryos, grown continuously
in monolayer at glass-liquid interface in standard culture medium.
Freshly dissociated tissue cells aggregated in 24 h into one or two large
masses; after growth in monolayer they formed smaller and more
numerous clusters and there were many free cells. The rate of change
was steepest after the first 2 days of growth in monolayer, then leveled
out, and after 6-7 days became almost stabilized, so that from then
on the tests yielded only minute clusters and free cells. As previously
found (Moscona, 1960), this tendency of cells modified by culture
in monolayers to form small clusters when tested by rotation persists
A . A . M O S C O N A
the cell surface which are removed or modified at dissociation; nonaggregation of differentiated cells could thus mean that such cells, in
being committed to, or engaged in, specialized biosynthetic activities,
are no longer able to regenerate their surface materials to their full
effectiveness; therefore, when removed from their native matrix, such
cells do not reconstitute the sort of surface that is essential for effective
mutual attachments. While these are undoubtedly oversimplified considerations, the phenomenon emphasizes clearly the dynamic nature of
cell contact and cell binding mechanisms, and particularly their correlation with functional or developmental states of the cells. It may be
appropriate to recall here that cells entering mitosis, and therefore
involved in specific metabolic tasks, round off, become temporarily
detached and show no contact inhibition (Abercrombie, 1958). It is
also of interest that changes in the biosynthetic patterns of cultured
cells due to infection with Rous virus are accompanied by decreased
adhesiveness (Rubin, 1961). In this connexion it should be stated that
decline in the ability to aggregate during development does not necessarily imply irreversible loss of cohesive competence: according to
Sigel, Scotti, Wryk and Dorsey (1959) cells from the kidney of the
adult monkey grown in monolayer for one passage produced nephric
aggregates when grafted to the brain.
The possibility of a significant relationship between the functional
state of cells and their adhesive properties is further suggested by
studies on cells which have been first grown as monolayers. Dissociated
embryonic cells grown in monolayer cultures were harvested periodically and tested by rotation for their capacity for aggregation; it was
found that this declined progressively, the change being most striking in
the first 2-4 days, then leveling off (embryonic retina, skin cells:
Moscona, 1960; cartilage cells: Kuroda, 1963). The rate of decline,
measured as decrease in size of aggregates, varied for the different types
of cells tested, and according to the age of the donor embryo, the conditions of culture, and the completeness of initial monolayering.
Kuroda (1963) studied aggregation by rotation of trypsin-dissociated
cells from the long bones of 13-day chick embryos, grown continuously
in monolayer at glass-liquid interface in standard culture medium.
Freshly dissociated tissue cells aggregated in 24 h into one or two large
masses; after growth in monolayer they formed smaller and more
numerous clusters and there were many free cells. The rate of change
was steepest after the first 2 days of growth in monolayer, then leveled
out, and after 6-7 days became almost stabilized, so that from then
on the tests yielded only minute clusters and free cells. As previously
found (Moscona, 1960), this tendency of cells modified by culture
in monolayers to form small clusters when tested by rotation persists