Control of cell proliferation is a fundamental aspect of tissue physiology
central to morphogenesis, wound healing and cancer. Although many of the
molecular genetic factors are now known, the system level regulation of growth
is still poorly understood. A simple form of inhibition of cell proliferation
is encountered in vitro in normally differentiating epithelial cell cultures
and is known as "contact inhibition". The study presented here provides a
quantitative characterization of contact inhibition dynamics on tissue-wide and
single cell levels. Using long-term tracking of cultured MDCK cells we
demonstrate that inhibition of cell division in a confluent monolayer follows
inhibition of cell motility and sets in when mechanical constraint on local
expansion causes divisions to reduce cell area. We quantify cell motility and
cell cycle statistics in the low density confluent regime and their change
across the transition to epithelial morphology which occurs with increasing
cell density. We then study the dynamics of cell area distribution arising
through reductive division, determine the average mitotic rate as a function of
cell size and demonstrate that complete arrest of mitosis occurs when cell area
falls below a critical value. We also present a simple computational model of
growth mechanics which captures all aspects of the observed behavior. Our
measurements and analysis show that contact inhibition is a consequence of
mechanical interaction and constraint rather than interfacial contact alone,
and define quantitative phenotypes that can guide future studies of molecular
mechanisms underlying contact inhibition