Membrane-deforming Molecules for Transportation and in vivo Delivery
In cellular activities, various dynamic functions such as material transport and signal transduction are realized by membrane deformation of the cell membrane composed of phospholipids. If such membrane deformation of liposomes can be artificially realized and controlled, it will be possible to develop attractive functional materials that mimic cellular activities. However, conventional membrane deformation is performed by heating or osmotic pressure application, which is difficult to apply in a biological environment.
In our laboratory, we are developing molecular materials that undergo various membrane deformations under physiological conditions by designing artificial molecules inspired by biological motifs such as membrane proteins. Based on this technology, we are challenging to construct "materials science using membrane deformation.
When cells take up biomacromolecules from the outside of the cell, they perform endocytosis, which causes the membrane to cave inward. We have succeeded for the first time in developing AzoMEx, a light-driven molecule that drives membrane deformation similar to endocytosis. When AzoMEx, a molecular machine that expands the membrane in response to blue light, was incorporated into liposomes and irradiated with light, endocytosis-like fission was induced from the outside to the inside of the liposomes. When endocytosis-like division is induced in the presence of a virus that interacts with AzoMEx, the virus is highly efficiently encapsulated inside the liposome and protected from the external environment. By taking advantage of the protective effect, we have also succeeded in the in vivo delivery of the encapsulated virus. AzoMEx, a molecule that enables active substance transport, is expected to have a wide range of biological applications as a deformable membrane material that enables the incorporation of various substances, from small to large molecules, into liposomes for in vivo transport. (Journal of the American Chemical Society 2023)