Cells in the body, such as macrophages and osteoclasts, have the remarkable ability to reshape themselves to perform essential tasks. Macrophages are immune cells that defend the body by swallowing harmful microbes or cleaning up dying cells, while osteoclasts are large bone cells that help maintain healthy bones by breaking down old bone tissue. The mystery of how these cells so quickly change their form has long fascinated scientists. A new study by Dr. Jiro Takito and Dr. Naoko Nonaka from Showa Medical University shows that special structural patterns called actin waves may be the key. Their work is published in the International Journal of Molecular Sciences.
Dr. Takito explained the motivation for the research: “Phagocytes carry out their functions by organizing new subcellular structures. During phagocytosis, macrophages internalize and degrade pathogens and apoptotic cells by forming the phagocytic cup and phagosome (Fig. A). Osteoclasts resorb bone by forming the sealing zone and ruffled border at the ventral membrane”. Phagocytosis is the process by which cells swallow and digest unwanted material, and apoptotic cells are simply dying cells that the body needs to remove.
When macrophages encounter foreign material at two-dimensional environment, they generate moving wsaves made of actin, a structural protein that helps shape the cell (Fig. B). These waves ripple across the surface, reorganizing the actin cortex and remodeling the membrane endoskeleton. As the waves travel, they separate the inner area of the cell surface from the outer edge, creating zones that can take on new roles (Fig. C). In simpler terms, these waves carve out new apparatus on the cell’s surface that are better suited for grabbing and digesting what the cell needs to remove.
Scientists pointed out a striking resemblance between the structures built by these actin waves in macrophages and those formed in osteoclasts during bone renewal. The sealing zone in osteoclasts, a thick ring that allows them to attach to bone, is very similar to the constriction zone in macrophages. Both rely on small cellular structures known as podosomes, which are tiny attachment points that help cells stick to and push against surfaces, and on a constantly changing actin network. This suggests that despite performing very different jobs—immune defense versus bone remodeling—both cell types may be relying on the same basic principle.
Dr. Takito and Dr. Nonaka discuss how these structures come together in layers, starting from tiny, fast-moving cycles of actin that last only seconds (Fig. D). These cycles build into larger waves that last minutes, and eventually into bigger zones that can stay active for hours or even days. This layering process allows the cell to remain flexible while still forming strong and lasting structures. As Dr. Takito explained, “dynamic structures formed from actin waves are organized through the fractal integration of self-organized, oscillatory substructures, with F-actin treadmilling fueling their formation and maintenance”. F-actin treadmilling refers to a process where actin filaments grow at one end while shrinking at the other, generating the force via mechano-chemical coupling.
Dr. Takito and Dr. Nonaka believe that these findings go far beyond immune cells and bone cells. Other cell types, such as skin cells or nerve cells, also use actin waves when they need to change shape, move, or divide tasks within their structure. For osteoclasts, this helps explain how bone is continuously renewed and kept healthy. For macrophages, it reveals how immune cells are able to adjust their surface so quickly to capture and destroy harmful particles.
Experts note that the bigger lesson here is that actin waves represent a universal principle in biology. Cells use them to organize themselves without needing external instructions. Understanding this principle may help scientists in the future develop treatments for diseases where immune responses or bone balance go wrong, such as infections or osteoporosis. By showing how rippling patterns of activity on a tiny scale can shape larger cell behavior, this study brings new clarity to how life’s smallest units stay so dynamic.
Journal Reference
Takito J., Nonaka N. “Formation of Membrane Domains via Actin Waves: A Fundamental Principle in the Generation of Dynamic Structures in Phagocytes.” International Journal of Molecular Sciences, 2025; 26(10):4759. DOI: https://doi.org/10.3390/ijms26104759
