HMN 2026: How Self-propelled actin filaments may explain how cells change shape spontaneously

Cells can spontaneously change shape even without external signals, but the underlying mechanisms behind this form of self-organization have remained unclear. Now, researchers from Japan have discovered self-propelled treadmilling actin filaments (SpTAs), mobile protein assemblies that function as self-propelled particles. The team’s work shows that even though SpTAs move randomly, they push the cell membrane outward to grow protrusions, thereby defining the overall shape of the cell. The work appears in EMBO Reports.

Every time a white blood cell engulfs a bacterium, a neuron extends a projection to connect with a neighboring cell, or a cancer cell forcefully squeezes through tissue to spread, the cell must change its shape to accommodate the movement. This transformative process, known as morphogenesis, depends largely on the protein actin, which forms a dynamic internal skeleton capable of pushing against the cell membrane from the inside. Understanding how actin drives morphogenesis is fundamental to improving our understanding of cells and diseases.

Scientists have long known that shape changes driven by actin are often guided by signals from outside the cell. These external signals activate proteins that control the site of actin filament growth and reorganization. However, cells can also form protrusions and adopt new shapes even without obvious external signals.

This ability to self-organize has remained a deep mystery of cell biology. How can the seemingly random movements of molecules inside a cell drive actin-based morphogenesis?

Tracking actin in living cells

To this end, a research team from Nara Institute of Science and Technology, Japan, examined how actin behaves inside living cells. Their study reveals a previously unrecognized form of actin self-organization that may help explain how cells spontaneously generate shape and movement.

The researchers focused on human glioma cells, which can spontaneously migrate even without any external signals. Using high-resolution live-cell microscopy, they observed assemblies of actin filaments moving throughout the cells.

Unlike previously described actin waves, which were thought to spread through cells as propagating chemical reactions, these structures behaved more like individual moving objects, similar to self-propelled particles studied in physics.

Filaments that move themselves

Through careful analysis, the researchers found that this movement is powered by treadmilling. During this process, actin monomers (the building blocks) are continuously added to the front of the filament by polymerization and shed from the rear through disassembly, consuming cellular energy to propel the filament assembly forward. Thus, the team named these structures self-propelled treadmilling actin filaments (SpTAs).

Further experiments and computational modeling showed that when SpTAs reach the cell membrane, they push it outward, forming a small protrusion. Then other SpTAs begin to accumulate at the site, which in turn drives the protrusion to grow further.

“We discovered SpTA and established the assembly of actin filaments as a novel class of biological active particles, solving the mystery of biological self-organization and providing new insights into how molecular-scale motion orchestrates complex higher-order organization,” Yagami said.

Overall, these results not only shed light on an important cellular process but also have broad interdisciplinary implications.

“We expect our findings to serve as a bridge connecting modern biology and modern physics to tackle the enduring puzzle of self-organization,” Inagaki concludes.

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