Using simple artificial cells, a research group led by Makito Miyazaki of the RIKEN Center for Integrative Medical Sciences (IMS) in Japan have uncovered fundamental physical principles that govern how living cells change their shape. By combining experiments with computer simulations and theoretical analysis done in collaboration with Purdue University, the researchers showed how a cell’s actin cytoskeleton—the network of protein fibers that gives it is shape—can generate cell-scale shape changes and front-rear polarity without relying on complex biochemical signaling. These findings, published in Science Advances, provide insights into biological processes such as cell migration, cell division, and embryonic development, and could help advance the development of artificial cells for applications ranging from drug discovery and regenerative medicine to synthetic biology—the creation of biological systems.

A system of artificial cells to study cell morphogenesis

Cells constantly change shape as they move, divide, and assemble into tissues during development. Although these changes in shape are essential for life, how they happen remains largely unknown as living cells contain thousands of molecules that act simultaneously. To reveal the fundamental principles, the research group built an artificial cell system using liposomes—cell-like structures that have a membrane but no cell mechanisms—encapsulating purified cytoskeletal proteins, creating a simplified and precisely controllable model of a living cell.

They combined this artificial cell system with large-scale computer simulations and theoretical analysis to link molecular interactions within the actin cytoskeleton to changes in cell shape. The artificial cells allowed them to investigate how the cell membrane changes shape in a way that is impossible in living cells, where the complexity of biological processes often masks the underlying physical mechanisms. This system itself is an important technological advance, providing a minimal, quantitatively controllable way to study cellular morphogenesis. Beyond its value as a research tool, it also marks an important milestone toward the development of autonomous artificial cells.

The discovery

During cell migration, structures in the front of a cell choose the migration path and those in the back push the cell forward. These structures develop from membrane blebs, which are bubble-like protrusions of the cell membrane. Using this new system, the researchers discovered that when the artificial cells were physically manipulated in a specific way, they consistently developed a single membrane bleb, demonstrating that front-rear polarity in a cell can emerge spontaneously through the mechanical properties of the actin cytoskeleton alone. This means that one of the defining characteristics of living cells can arise from simple physical interactions, without requiring biochemical signaling or pre-existing asymmetry.
As Miyazaki explains, "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.”

What else can this artificial cell system be used for?

Artificial cells could be used as simplified models for uncovering other fundamental principles of life while also offering a foundation for future technologies. With more advances, these cells could become programmable microscopic systems capable of sensing their surroundings, delivering therapeutic molecules to diseased tissues, manufacturing useful compounds, or even repairing damaged tissues.

Moving forward

"Our goal was to understand how the remarkably complex behavior of living cells can emerge from simple physical interactions," says Miyazaki. “By identifying the physical rules that govern cell shape, the present study lays important groundwork for numerous future applications.”

Miyazaki and his team are now focusing on reconstructing increasingly sophisticated cellular behaviors, bringing artificial cells a step closer to practical applications in medicine, biotechnology, and synthetic biology.