James' World 2

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No one saw the blob takeover coming. In 2009 a team of biophysicists led by Anthony A. Hyman of the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, Germany, were studying specklelike structures called P granules in the single-celled embryo of a tiny, soil-dwelling worm. These specks were known to accumulate only at one end of the cell, making it lopsided so that, when it divides, the two daughter cells are different. The researchers wanted to know how that uneven distribution of P granules arises.

They discovered that these blobs, made from protein and RNA, were condensing on one side of the cell like raindrops in moist air, and dissolving again on the other side. In other words, the molecular components of the granules were undergoing phase transitions like those that switch a substance between liquid and gas.

That was a weird thing to be happening in cell biology. But at first it seemed to many researchers little more than a quirk and didn’t excite much attention. Then these little blobs—now called biomolecular condensates—began popping up just about anywhere researchers looked in the cell, doing a myriad of vital tasks.

Biologists had long believed that bringing order and organization to the chaos of molecules inside a cell depended on membrane-bound compartments called organelles, such as the mitochondria. But condensates, it turns out, offer “order for free” without the need for membranes. They provide an easy, general-purpose organization that cells can turn on or off. This arrangement permits many of the things on which life depends, explains biophysicist Petra Schwille of the Max Planck Institute of Biochemistry in Martinsried, Germany.

These little blobs inside living cells now appear to feature across all domains of the living world and are “connected to just about every aspect of cellular function,” says biophysical engineer Cliff Bran­gwynne, who was part of the 2009 Dresden team and now runs his own lab at Princeton University. They protect cells from dangerously high or low temperatures; they repair DNA damage; they control the way DNA gets turned into crucial proteins. And when they go bad, they may trigger diseases.

Biomolecular condensates now seem to be a key part of how life gets its countless molecular components to coordinate and cooperate, to form committees that make the group decisions on which our very existence depends. “The ultimate problem in cell biology is not how a few puzzle pieces fit together,” Brang­wynne says, “but how collections of billions of them give rise to emergent, dynamic structures on larger scales.”

These ubiquitous specks have “completely taken over cell biology,” says biophysicist Simon Alberti of the Technical University of Dresden. The challenge now is to understand how they form, what they do—and perhaps how to control them to devise new medical therapies and cures.

Initially researchers studying condensates thought they formed by coalescing as one liquid phase became insoluble in another—like vinegar droplets in the oil of salad dressing. But condensates aren’t always simply phase-separated liquids.

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Mark Ross

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