These findings could help researchers design proteins with stabilities carefully tuned to their needs. In many industrial processes that involve bacteria, for instance, raising the temperature increases yield — but before too long the bacteria die from the trauma of heat. It will be interesting to see if we can stabilize a bacterium by making those few proteins that disintegrate early more resistant to temperature, Picotti said.

Beyond all these observations, however, the group’s wealth of information about how easily each protein unfolds has some biologists especially excited. A protein’s stability is a direct measure of how likely it is to form aggregates: clumps of unfolded proteins that stick to each other. Aggregates, often a nightmare for the cell, can interfere with essential tasks. For instance, they are implicated in some serious neurological conditions, such as Alzheimer’s disease, in which plaques of denatured proteins gum up the brain.

But that doesn’t mean aggregation occurs only in individuals suffering from these conditions. On the contrary, investigators are realizing that it may be happening all the time, without obvious stressors, and that a healthy cell has ways of dealing with it. “I think this is increasingly recognized as a very common phenomenon,” said Michele Vendruscolo, a biochemist at the University of Cambridge. “Most proteins actually misfold and aggregate in the cellular environment. The most fundamental information obtained by Picotti is about the fraction of time in which any given protein is in its unfolded state. This fraction determines the degree to which it will aggregate.” Some proteins almost never unfold and aggregate, others do it only in certain situations, and still others do it constantly. The new paper’s detailed information will make it much easier to study why these differences exist and what they mean, he said. Some of the denaturing curves even show patterns that suggest the proteins were aggregating after they unfolded. “They’ve been able to monitor both steps — both the unfolding and the subsequent aggregations,” Vendruscolo said. “That’s the excitement of this study.”

While many scientists are interested in aggregates because of the damage they cause, some are thinking about the phenomenon from another angle. Drummond said it has become clear that some aggregates are not just wads of trash floating around the cell; rather, they contain active proteins that continue to do their jobs.

Imagine that from a distance, you see smoke billowing out of a building, he said. All around it are forms that you take to be bodies, dragged from the wreckage. But if you get closer, you may find that they’re actually living people, who escaped from the burning building and are waiting for the emergency to pass. That’s what’s happening in the study of aggregates, Drummond said: Researchers are finding that instead of being casualties, proteins in aggregates may sometimes be survivors. “In fact, there is a whole field that is now exploding,” he said.

Rather than being just a sign of damage, the clumping may serve as a way for proteins to preserve their function when the going gets tough. It might help protect them from the surrounding environment, for instance. And when conditions improve, the proteins could leave the aggregates and refold themselves. “They have temperature-sensitive [shape] changes that, if you don’t look too closely, look like misfolding,” Drummond said. “But there’s something else going on.” In a 2015 Cell paper, he and collaborators identified 177 yeast proteins that seem to regain function after being cloistered in aggregates. In a paper that appeared this past March, his team found that altering one of these proteins so that it couldn’t aggregate actually caused serious problems for the cell.

All in all, this work suggests that proteins are curiously dynamic structures. At first they might look like rigid machines, at work on fixed tasks for which one specific shape suits them. But in fact, proteins may morph into several different forms in the course of their normal duty. And in times of need, their shapes may alter so radically that they look as though they are expiring, when they are really fortifying themselves. At the molecular level, life may consist of constantly coming together and falling apart.

This article was reprinted on TheAtlantic.com.