Self-propelled actin filaments: Novel structures driving spontaneous cell morphogenesis

Ikoma, Japan—Every time a white blood cell engulfs a bacterium, a neuron extends a projection to connect with a neighboring cell, or when 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 improve 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?

To this end, a research team led by Professor Naoyuki Inagaki, along with Dr.  Kio Yagami and Assistant Professor Takunori Minegishi, Assistant Professor Kentarou Baba, Mr. Shinji Misu, Dr. Hiroko Katsuno-Kambe, Dr. Kazunori Okano, Professor Yuichi Sakumura, and Professor Yoichiroh Hosokawa, all from Nara Institute of Science and Technology, Japan, examined how actin behaves inside living cells. Their study, which will be published in EMBO Reports on June 25, 2026, 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.

Through careful analysis, the researchers found that this movement is powered by treadmilling. During this process, actin monomers (the building blocks) are continuously added at 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 modelling 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,” remarks Dr. Yagami.

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,” concludes Professor Naoyuki Inagaki.

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Resource

Title: Spontaneous membrane protrusion and cell morphogenesis via self-propelled actin filaments

Authors: Kio Yagami, Takunori Minegishi, Kentarou Baba, Shinji Misu, Hiroko Katsuno-Kambe, Kazunori Okano, Yuichi Sakumura, Yoichiroh Hosokawa, and Naoyuki Inagaki

Journal: EMBO Reports

DOI: 10.1038/s44319-026-00804-6

Information about the Laboratory of Systems Neurobiology and Medicine can be found at the following website: https://www.naist.jp/iri/inagaki/english/

About Nara Institute of Science and Technology (NAIST), Japan

Established in 1991, Nara Institute of Science and Technology (NAIST) is a national university located in Kansai Science City, Japan. In 2018, NAIST underwent an organizational transformation to promote and continue interdisciplinary research in the fields of biological sciences, materials science, and information science. Known as one of the most prestigious research institutions in Japan, NAIST lays a strong emphasis on integrated research and collaborative co-creation with diverse stakeholders. NAIST envisions conducting cutting-edge research in frontier areas and training students to become tomorrow's leaders in science and technology.