hysteresis{27}

Just three weeks out from the start of the semester and nagging thoughts of cell biology are already creeping into my day dreams. Shortly after our cell and molecular biology course completed last year, I shut down my experimental cell biology research program to focus full time on being a science educator rather than a scientist. I spent the last of my grant dollars from the National Institutes of Health, hung up my lab coat, and shut the door to Derring 5029 where I had spent the most – and some of the best- waking hours of my career. Based on what I know about the ‘rules’ of an academic research career, I’m fairly certain there is no turning back on this decision – or is there? Which brings me to hysteresis.

Hysteresis is an irreversible, switch-like behavior that can occur between two steady-states in a system. The state in which a system resides depends not only on the current conditions, but also on the history of the system.  Here are a few classic examples:

rubber bands: With no force applied, a rubber band exists stably in its unstretched state. However, once stretched beyond a certain point, the rubber band is permanently stretched, even when the force is removed. Same conditions, different state, depending whether the rubber band had experienced a threshold stretching. Importantly, hysteretic transitions are considered to be essentially irreversible.

some solid-liquid transitions: Think about Jello. After you dissolve the gelatin in boiling water, Jello won’t solidify unless you refrigerate it. However, once it is solid, Jello can sit out at room temperature and it will remain solid (except maybe in August).

Hysteretic transitions are not truly irreversible. However, the energy required to push a system into a particular steady state is much greater than what is required to keep it in a steady state. It’s nature’s way of preventing slippage. Thermostats are designed with this principle in mind. Otherwise, a climate control system would be switching back and forth between heating and cooling mechanisms to maintain a room at exactly 25°C.

As a cell biologist, my most rewarding work was testing the prediction of my colleagues John Tyson and Bela Novak, that cell division was regulated by hysteresis. When cells commit to the cell cycle, the process by which they duplicate their DNA precisely and other cell contents less precisely, then divide into two daughter cells, the commitment is irreversible. Cells  may pause or even arrest the cell cycle if something is wrong, but the cell cycle never moves in reverse. Both my students and my colleague and friend Joe Pomerening found compelling evidence for John and Bela’s theoretical predictions of hysteresis. Cells synthesize a protein called cyclin, and a threshold concentration is required to drive the cell into mitosis, the final stage of the cell cycle where cell division occurs. In order to exit mitosis, the level of cyclin must drop to a distinct inactivation threshold concentration that is measurably below the activation threshold.

The cell cycle example illustrates that the state transitions are not truly irreversible, but in essence, may require a bigger ‘push’ to get out of one state, than was required to get into that state in the first place. When there are certain types of feedback, a system can oscillate between one state and the other in what is called a hysteresis loop. This is what happens with the cell cycle.

Does hysteresis only exist in the natural world? Wikipedia has a pretty good description of the phenomenon, including examples from economics (e.g. unemployment levels) that are described as hysteretic.

Which makes me wonder, which of life’s transitions are hysteretic and which are not?

Closing a research program? Probably hysteretic. Not impossible to go back but the deck would be stacked heavily against an investigator with a significant gap in her funding record, more so than a young scientist applying for her first grant.

Becoming a parent? Definitely hysteretic. There’s really no turning back from that one, but who would want to?

Marriage? In contemporary society, marriage hardly seems hysteretic, and to be honest, I prefer to view marriage as an unstable, rather than stable, steady state. That view keeps me intentional about what it means to be a loving and committed spouse rather than taking the relationship  for granted.

In the past few months, and more pointedly in the past few days, I have the unsettling sensation that I am in the midst of a professional hysteretic transition, moving from one stable steady state to the next. Graphically, hysteretic transitions appear as jumps, sharp transitions, never as gently sloping curves.

from Sha et al., 2003

The ride has not been entirely pleasant, the transition not anticipated in time to fasten my seat belt, and I’m not quite sure where I’m headed. I’ve even tried to turn back, but find that I cannot. I’m propelled, which is thrilling and terrifying at the same time. I’ll report back when I land.

….. one more thought on hysteresis. As one approaches a hysteretic transition, a phenomenon known as “critical slowing down” occurs. John was convinced that we would find evidence of critical slowing down in the cell cycle. While the theoretical predictions were compelling, it was hard, damn hard, to generate experimental evidence. Here it is:

evidence for “critical slowing down” in the cell cycle

If you are not impressed at the precision it took to achieve this evidence, believe me that Wei Sha, whose data are shown here, and Joe Pomerening  are among the few individuals in the world who could have done this experiment.

Critical slowing down? That may explain a few things in my life as well. I’ve been trying to fight that aspect of the transition too, but perhaps resistance is futile.