Artificial Cells Reveal How Living Cells Change Shape

A research group led by Makito Miyazaki of the RIKEN Center for Integrative Medical Sciences has used simple artificial cells to uncover fundamental physical principles behind how living cells change shape. Working with Purdue University, the team combined experiments, computer simulations, and theoretical analysis to show that a cell's actin cytoskeleton, the network of protein fibers that gives it structure, can generate cell-scale shape changes and front-rear polarity on its own, without complex biochemical signaling. The findings, published in Science Advances, offer insight into processes such as cell migration, cell division, and embryonic development, and could support the development of artificial cells for uses ranging from drug discovery and regenerative medicine to synthetic biology.

Cells are constantly changing shape as they move, divide, and organize into tissues, but because living cells contain thousands of molecules acting at once, how these shape changes happen has largely remained unclear. To isolate the underlying mechanisms, the researchers built an artificial cell system using liposomes, cell-like structures with a membrane but no internal cell machinery, and filled them with purified cytoskeletal proteins to create a simplified, precisely controllable stand-in for a living cell. Pairing this system with large-scale simulations and theoretical modeling let them connect molecular interactions within the actin cytoskeleton directly to changes in cell shape, something the complexity of real cells tends to obscure. The system itself represents a technical advance, offering a minimal, quantitatively controllable way to study cell morphogenesis, and a step toward autonomous artificial cells.

During cell migration, front structures set the direction of movement while structures at the rear push the cell forward, both arising from membrane blebs, bubble-like protrusions of the cell membrane. When the researchers physically manipulated the artificial cells in a specific way, the cells consistently formed a single membrane bleb, showing that front-rear polarity can emerge spontaneously from the mechanical properties of the actin cytoskeleton alone, without biochemical signaling or any pre-existing asymmetry. As Miyazaki explained, “By reconstructing membrane morphogenesis from purified proteins, we showed that local interactions within the actin cytoskeleton are sufficient to generate large-scale changes in cell shape.”

Beyond serving as a model for uncovering other basic principles of life, the researchers say artificial cells could eventually evolve into programmable microscopic systems able to sense their surroundings, deliver therapeutic molecules, manufacture useful compounds, or repair damaged tissue. “Our goal was to understand how the remarkably complex behavior of living cells can emerge from simple physical interactions,” Miyazaki said. “By identifying the physical rules that govern cell shape, the present study lays important groundwork for numerous future applications.” The team is now working to reconstruct more sophisticated cellular behaviors, moving artificial cells closer to practical use in medicine, biotechnology, and synthetic biology.