Checking how cells grow

New research dismisses a widely held assumption about how cells grow

Research published today in Journal of Biology challenges an assumption about cell growth that underpins modern cellular biology. Ian Conlon and Martin Raff, of University College London, show that mammalian cells do not regulate their size in the way scientists have assumed they do since the 1970s.
Conlon and Raff conducted a series of experiments, using Schwann cells from the sciatic nerve of rats, to establish how mammalian cells control their size and ‘decide’ when to divide. This processes of cell size, growth and division has been widely studied in yeast for thirty years, and many aspects are the same in the two types of cell. Both yeast and mammalian cells are known to be able to maintain a constant average size as they grow and divide. It has therefore been assumed that the ‘checkpoints’ yeast cells use to ensure that they divide when they reach the correct size are mirrored by checkpoints in mammalian cells, but that assumption had not been tested experimentally – until now.

Using precise measurements, Conlon and Raff found key differences in the ways yeast and mammalian cells grow. Yeast cells grow exponentially, doubling in size over a fixed time period, but mammalian cells grow in a linear way, getting larger by the same amount each day; this means that the rate at which mammalian cells grow is the same regardless of the cell’s size, whereas in yeast big cells grow faster than small ones.

Previous research had shown that when moved to a nutrient-rich environment, yeast cells adjust quickly – within one cycle of growth and division. The average size of the cells increases when there are more nutrients available – so, yeast uses cell-size checkpoints to determine how large the cell should be before it divides.

It had been assumed that mammalian cells also use cell-size checkpoints. But Conlon and Raff found that when mammalian cells were moved to a nutrient-rich environment, it took approximately six divisions before cells grew to the average size they expected. This led them to conclude that mammalian cells do not use checkpoints based on their size to determine when to divide. Instead, Conlon and Raff suggest that mammalian cells ‘talk’ to each other, using extracellular signalling, to determine how large they should grow and when they should divide. “Animal cells hardly do anything without signals from other cells” says Raff.

The new research makes clear that there are important differences between the way yeast and mammalian cells coordinate cell growth and size. These differences make sense biologically. Yeast is a single-celled organism – cells are independent of each other and can grow and divide as fast as the nutrients in their environment can support. Animal cells are part of a larger organism, so their growth affects the good of the whole animal, and it makes good biological sense that this is controlled by signals from other cells.

Understanding cell growth and proliferation is of profound importance for biology and has implications for tackling disease, including cancer.