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Controlled phase separation in membranes

 Illustration of an anchored metalloenzyme and membrane domains of different sizes

An artificial metalloenzyme (orange-brown structure) anchored to the surface of lipid membranes allows lateral phase separation in membranes to be specifically controlled (represented by light blue and pink areas). Targeted genetic optimization of the enzyme can lead to the formation of larger membrane domains, which can result in cell budding due to the different curvatures of the membranes. (Image: R.Hamaguchi, Institute of Science, Tokyo)

Cell membranes consist of a mixture of different lipids and proteins. These are not always evenly distributed. Under certain conditions, similar lipids and proteins can accumulate laterally in small areas within the membrane. This phase separation creates functional zones within the membrane that play a key role in many biological processes, including signal transmission and transport.

A team of researchers from the SNI network has now shown for the first time that such lateral phase separation in membranes can be specifically controlled by a chemical reaction. This is made possible by the use of an artificial metalloenzyme anchored to the surface of the lipid membrane. This enzyme catalyzes ring-closing olefin metathesis (RCM) – a reaction in which the researchers use a tailored substrate that releases a small molecule (decanoic acid) after catalysis. This molecule spontaneously inserts into the lipid bilayer, thereby altering the membrane composition, curvature and ultimately its structure.

Through targeted genetic optimization of an artificial metalloenzyme, the team led by Prof. Thomas Ward (Department of Chemistry, University of Basel) and Prof. Kazushi Kinbara (Institute of Science, Tokyo) achieved a threefold increase in reaction rate and induced the formation of larger membrane domains. Because these domains exhibit distinct curvatures, the metalloenzyme-catalyzed reaction ultimately triggered cell budding – the mechanism of cell division observed in yeast. These findings provide new insights into an alternative pathway for triggering cell division, a fundamental process of Life.

The paper, recently published in the Journal of the American Chemical Society, highlights how chemical catalysis can be used to dynamically control membranes – an important step toward “smart” artificial vesicles.

Original publication
Programmable Artificial-Cellular Membrane Dynamics via Ring-Closing Metathesis
Rei Hamaguchi, Damian Alexander Graf, Kazushi Kinbara, Thomas R. Ward
J. Am. Chem. Soc. 2025
https://doi.org/10.1021/jacs.5c10187

Research group Prof. Thomas Ward
https://ward.chemie.unibas.ch/en/research/

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