Researchers in Japan create interlocking propellor-shaped molecules for forming stable islands in functional lipid membrane materials

Osaka, Japan – Cells are enclosed by a cell membrane, which is a sophisticated structure mainly made of lipids and is vital for fundamental biological processes. Artificial lipid membranes have many practical applications, such as drug delivery, but engineering the properties of these membranes is a huge challenge. Now, a team in Japan has found a new way to control the membrane structure.

In work to be published in the Journal of the American Chemical Society, researchers at the University of Osaka, Gunma University and Kyushu University have created a propellor-shaped lipid mimic molecule (called triptycene) that interlocks to make stable “islands” in “sea” of lipid (lipid membrane).

Lipid molecules that form cell membranes have a water-loving head and an oil-loving tail. The molecules self-assemble into a double layer, called a bilayer, with the tails pointing to the middle of the bilayer and the heads forming the surfaces. Natural membranes contain many types of lipids with different functions. In a process called phase separation, lipids of the same type group together to form “islands”, known as domains, with distinct properties.

Phase separation is fundamental to vital cell functions, and artificial membranes with domains have different properties from those with uniformly distributed components. Therefore, understanding and manipulating phase separation is key to improving artificial lipid membrane materials. However, lipids mix easily, and it is difficult to form thermally stable lipid domains in an artificial lipid membrane.

“To get lipid molecules of the same type to cluster together in a membrane, they need to interact with each other specifically,” says one of main authors Takayuki Iwata. “We thought that we could form these lipid domains by exploiting the tendency of a molecule shaped like a propellor with three blades to self-assemble.”

The researchers made a new lipid mimic molecule, the most effective of several designs tested, by attaching the propellor-shaped molecule to oil-loving tails and a water-loving head, so that the tails slotted into the membrane and the head formed part of the membrane surface.

“The propellor-shaped moiety interlocked with each other like gears and the surrounding lipids fitted into the gaps between them, which is a new way of achieving phase separation,” adds another main author Masanao Kinoshita. “The strong interlocking and incorporation of the other lipids also meant that our lipid mimic formed really stable domains in the membrane.”

In fact, the artificial membranes kept their lipid mimic domains up to 58 °C, well above temperatures found in the body. This high thermal stability could be useful in practical applications.

The lipid mimic molecule could have uses in many types of functional membrane materials. Creating domains on an artificial membrane could concentrate catalysts or other functional molecules in specific areas, which could be used to create membranes for catalyzing chemical reactions, capturing specific molecules, or delivering drugs. The new design principle of using interlocking lipid mimic molecules adds a valuable tool for engineering domains in artificial membrane materials.
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The article, “Triptycene-Based Lipid Mimics for Thermally Stable Membrane Phase Separation,” was published in the Journal of the American Chemical Society at DOI: https://doi.org/10.1021/jacs.6c05364

About The University of Osaka
The University of Osaka was founded in 1931 as one of the seven imperial universities of Japan and is now one of Japan's leading comprehensive universities with a broad disciplinary spectrum. This strength is coupled with a singular drive for innovation that extends throughout the scientific process, from fundamental research to the creation of applied technology with positive economic impacts. Its commitment to innovation has been recognized in Japan and around the world. Now, The University of Osaka is leveraging its role as a Designated National University Corporation selected by the Ministry of Education, Culture, Sports, Science and Technology to contribute to innovation for human welfare, sustainable development of society, and social transformation.
Website: https://resou.osaka-u.ac.jp/en