An active size-sensing mechanism may control the cell cycle in mammalian cells, according to a letter in Nature Cell Biology this week. A size threshold adjusts cell cycle length in the next cycle to ensure maintenance of a proper balance between growth and proliferation rates in various vertebrate cell types including human, mouse, and chicken erythroblasts and fibroblasts in vitro, Ernst Müllner and colleagues at the Department of Medical Biochemistry at the Vienna Biocenter found in their study.

The question of whether cells need an active size-sensing mechanism or whether they stochastically revert back to a mean size after several divisions following either chemical or signaling perturbation has been debated for about 40 years, said Müllner. "Our data would go to the camp of the people arguing for an active cell size sensing," he told The Scientist.

The team does not claim that a size-sensing mechanism is applicable to all animals, and they have no mechanistic proof for how this might be effected. But their data favor the interpretation that this is an active mechanism, Müllner said: "You need a cell to sense first if it is accumulating mass rapidly enough or that it has already accumulated a critical mass before getting permission to pass through a subsequent checkpoint… so that you get [the all-clear] to progress towards S phase."

Zhilin Qu, of the Cardiovascular Research Laboratory at the University of California, Los Angeles, noted that the concept had been demonstrated previously in yeast. Those studies pointed to two trends called "timer" and "sizer." "This paper actually demonstrates again that there is a 'sizer' and 'timer' in animal cells," said Qu, who wasn't involved in the study.

But the new data may only add to the confusion, because different papers have shown different results, said Savraj Grewal, postdoc in Bruce Edgar's lab in the Division of Basic Sciences at the Fred Hutchinson Cancer Research Center, who was not involved in the study. He said a number of different papers that performed similar kinds of experiments in different cells came to the entirely opposite conclusion, citing particularly Martin Raff's work on Schwann cells. Raff could not be reached for comment.

"The rate of their growth and the rate of their division were two separable and two independently controlled phenomena, so size was a net effect of how much growth and how much division there is to determine cell size," Grewal said.

Müllner acknowledged that the work is at odds with published data from Martin Raff's laboratory. "We have not yet done any experiments in our lab with Schwann cells, so it may be perfectly true that this is happening in [them]," he said.

"Does the question of cell size and measurement really depend on what cells you are talking about?" asked Grewal. In that case, the question was not so much "do animal cells have a size sensing mechanism?" but "do they need one?" he said.

The main question was what happens in vivo, where cells are growing with abundant nutrients and an array of different growth and mitogenic factors together with cell adhesion effects, Grewal said. "Maybe the minimum size threshold is never reached and they never have to worry about having minimum size to divide because the growth factors around are so abundant."

"What I think this paper did was to highlight how important it really is to study cell growth as opposed to cell division," said Grewal. "A lot of work has gone into understanding and unraveling the mechanisms that control cell division and cell cycle, and it is only now that people are taking the tools that we have to address how cell growth is regulated and how it is coupled to the cell cycle."