Using catalytic chemistry, researchers at Institute of Science Tokyo have achieved dynamic control of artificial membranes, enabling life-like membrane behavior. By employing an artificial metalloenzyme that performs a ring-closing metathesis reaction, the team induced the disappearance of phase-separated domains as well as membrane division in artificial membranes, imitating the dynamic behavior of natural biological membranes. This transformative research marks a milestone in synthetic cell technologies, paving the way for innovative therapeutic breakthroughs.
Programmable Artificial Cell Membranes Controlled by a Catalytic Chemical Reaction
Biological membranes are fundamental structures that form boundaries of all living cells, controlling how cells communicate, grow, and respond to their environment. These membranes are composed of different molecules, such as lipids and proteins, which organize themselves into a membrane layer. Under certain circumstances, the molecules cluster together into local functional regions that regulate specific biological processes. These clustered regions are known as phase-separated domains and are distinct from the surrounding membrane.
Understanding and replicating the dynamic behaviors of these regions has long fascinated scientists aiming to construct artificial cells that behave like natural cells. However, since most artificial membrane models remain static, reproducing these adaptive properties of biological membranes has remained a major challenge until now. Addressing this challenge, researchers at Institute of Science Tokyo (Science Tokyo), Japan, and the University of Basel, Switzerland, jointly developed a new chemical strategy to control the behavior of artificial cell membranes.
The study was led by Professor Kazushi Kinbara and doctoral student Rei Hamaguchi from the School of Life Science and Technology, Science Tokyo, Japan, in collaboration with Professor Thomas R. Ward from the University of Basel, Switzerland. The findings were made available online on October 15, 2025, and were published in Volume 147, Issue 43 of the Journal of the American Chemical Society on October 29, 2025.
To bring the membranes to life, the researchers first built tiny artificial cell-like structures called lipid vesicles. The researchers then built a hybrid catalyst known as an artificial metalloenzyme (ArM)-a combination of a biological protein streptavidin (Sav) and a synthetic metal catalyst (ruthenium metal complex) carrying a biotin (vitamin B7) moiety. This enzyme acts like a catalyst on the membrane, performing a critical chemical reaction known as ring-closing metathesis (RCM).
To attach the ArM catalyst to the surface of the lipid membrane, the team also incorporated a special kind of biotin-tagged lipid into the membrane, which acted as an anchor for the catalyst.
"When triggered by fatty acid precursors, the ArM system releases free fatty acids through RCM," explains Kinbara. "These fatty acids slip into the membrane, subtly altering its structure and driving dynamic membrane behavior."
Molecular simulations revealed key mechanisms underlying these transformations. Inactive, caged fatty acid precursors were first activated by the ArM catalyst through the RCM reaction. This reaction uncages the caged fatty acid precursors, releasing free fatty acids near the membrane. The released fatty acids naturally insert themselves into the membrane surface, changing its rigidity and curvature, which in turn leads to visible transformations such as the disappearance of phase-separated domains and membrane division.
"It's a bit like giving a synthetic membrane the ability to breathe and respond," says Kinbara. "By controlling a chemical reaction on the membrane's surface, we can make it reorganize itself, much like a living cell does."
The discovery marks the first attempt to chemically program the physical behavior of artificial membranes, setting the stage for the creation of life-like materials that can sense and respond to their surroundings. It not only advances synthetic biology but also introduces a blueprint for creating programmable artificial membranes that could inspire future therapeutic innovations-bridging the gap between chemistry and life.
Reference
- Authors:
- Rei Hamaguchi1, Damian Alexander Graf2, Kazushi Kinbara1,3*, and Thomas R. Ward2*
*Corresponding author
- Title:
- Programmable Artificial-Cellular Membrane Dynamics via Ring-Closing Metathesis
- Journal:
- Journal of the American Chemical Society
- DOI:
- 10.1021/jacs.5c10187
- Affiliations:
- 1 School of Life Science and Technology, Institute of Science Tokyo, Japan
2 Department of Chemistry, University of Basel, Switzerland
3 Research Center for Autonomous Systems Materialogy, Institute of Integrated Research, Institute of Science Tokyo, Japan
