‘Major advance’ shows how earthquake-like events may help cells move

 

Using meticulous biochemistry and minimal ingredients, researchers have re-created one of the weirdest materials inside animal cells, the actomyosin cortex—a meshwork of structural and motor proteins that give the cell shape and help it move.

In this artificial cytoskeleton and their matching simulations, the researchers observed rare, explosive energy releases, which they say resemble earthquakes and point to a fine-tuned mechanism for how cells “blow up” their cytoskeleton to reshape themselves.

Occurring only in networks with a particular structure, these unusual events are characteristic of self-organized criticality, the team concludes in a new study (Nat. Phys. 2025, DOI: 10.1038/s41567-025-02919-4).

 

Self-organized criticality is a once-popular idea that certain dynamic systems drive themselves toward critical events, such as sand piling up until it slides downhill or an earthquake releasing pent-up energy in Earth’s crust.

But observational and experimental evidence of self-organized criticality beyond these classic exemplars has been very difficult to come by, and many physicists now doubt its usefulness as the unifying model originally thought to explain how dynamic systems work across nature. But this study may have uncovered a microscopic example.

Inside the cellular machine

The cell’s actomyosin cortex has for decades defied biophysicists’ attempts to explain its lively behavior and surprising properties. Once thought to be a simple gel or like foam, the cortex is a very stiff yet adaptable network of flexible filaments, tiny molecular motors, and other proteins. A cell dismantles and rebuilds its cytoskeleton every 30 s, even when sitting idle, without the whole structure falling apart.

Biophysicists have pulled, poked, and prodded living cells to try to figure out how the cortex, which lies just beneath the cell membrane, works as a machine.

In 2016 researchers observed cells twitching and occasionally convulsing and dubbed these unexpectedly large and rare events “cytoquakes” for their statistical similarity to earthquakes. But further experiments and statistical tests by another team suggested that these cytoquakes were just chance outliers in a random process, not the hallmarks of self-organized criticality.

But these previous studies probed cells only from the outside, measuring the forces exerted by the cortex on flexible microposts. “We wanted to take a look inside the cell, so we re-created [its] intracellular machinery,” says study senior author Michael Murrell, a soft-condensed-matter physicist at Yale University.

In a chamber slide containing a glass coverslip coated with a membrane-like layer, the team mixed purified actin monomers with precise concentrations of two nucleation-promoting factors, Arp2/3 and formin, to grow networks of branched and straight F-actin filaments. Then they added fluorescent beads and myosin II dimers and imaged the lot.

The researchers measured how these artificial actomyosin networks moved using two methods: One tracked individual, fluorescently tagged subunits within the network, and the other captured displacements of the protein networks at large. Then they analyzed the behavior of their replica cortex and compared it with a simulation of polymerizing actomyosin networks.

Murrell’s team observed cytoquakes similar to those seen in living cells and that, they say, fit the statistical pattern of self-organized criticality.

Artificial networks branched by design

Moreover, the team observed these events only in networks of moderately branched, not straight or highly entangled, actin filaments. Based on their simulations, which showed the same patterns, the researchers think that this particular branched structure funnels mechanical stress into stiffer parts of the cytoskeleton, where it builds up until it is released in a sudden burst.

“There’s a very specific structure or organization in which this happens,” says Murrell. If the network is too branched and tangled, then myosin motors can’t assemble into larger complexes capable of exerting greater force on the actin filaments. But some degree of branching is required for critical collapses to occur, Murrell says.

“Say you’re clipping parts of a tree,” he says. “If you clip the ends of a branch, then tiny parts of the tree fall off. If you clip the base of the branch, the whole [limb] falls off.”

The team says this self-organized criticality allows cells to quickly dismantle and rebuild their cytoskeleton when they need to move. “It’s easier to make and destroy than to try and bend or reshape,” Murrell says.

John C. Crocker, a physicist studying soft and living matter at the University of Pennsylvania, finds the study “convincing” because of its meticulous biochemistry.

“They’ve managed to build up, piece by piece, building block by building block, this minimal recipe that actually recapitulates some of the behaviors of the cortex. And then they reproduced it in simulation as well,” he says. Their simulations also modeled the cortex on the same “meaningful” scale as their lab experiments, Crocker adds.

“That’s a real advance.”

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