Development of New 2D Materials that Spontaneously Transform into Vesicles
The results obtained by Professor Kim Yong-ju’s group were published in JACS.
Next-generation materials for drug and mRNA delivery were developed by mimicking the behavior of cell membranes, and the transformation mechanism was investigated.

▲ Professor Kim Yong-ju (left, corresponding author) and M.S. student Seo Gun-hee (right, first author) in the KU-KIST Graduate School of Converging Science and Technology.

Professor Kim Yong-ju’s group in the Department of Integrative Energy Engineering of KU and the KU-KIST Graduate School of Converging Science and Technology developed 2D supramolecule-based new materials that spontaneously transform from a 2D sheet structure to a 3D nano-vesicle structure, and investigated the mechanism.

* Supramolecule: A molecular complex that has a high-dimensional structure formed by the interactions between specific molecules.

* Vesicle: A particulate with an empty internal space.

Cell membranes are representative naturally-occurring 2D supramolecules formed by the self-assembly of lipid molecules. Cell membranes recognize changes in the external environment and change their structure and function spontaneously and reversibly according to that environmental change. Cell membranes perform various functions in the body through the reversible structural change between a 2D sheet structure and a 3D nano-vesicle structure. However, this intriguing behavior of cell membranes has not yet been accurately understood at the molecular level, limiting the ability to mimic cell membranes to develop multi-purpose materials.

In the study, the research group utilized the donor-acceptor interactions between two aromatic compounds with different π-electron densities to develop a new ultra-thin 2D material several micrometers long and 2 nm thick in an aqueous solution. The research group showed that the 2D sheet structure spontaneously changes its own structure by budding on the surface of the sheet material and ultimately transforms into nano-vesicles of highly uniform size. In this way, a new, next-generation material was developed by closely mimicking cell membrane behavior.
* Donor-acceptor interaction: An interaction between a relatively electron-rich molecule and an electron-poor molecule.

The research obtained accurate understanding of molecule-level behavior by using various spectrometric methods, such as nuclear magnetic resonance spectroscopy and ultraviolet absorption spectrophotometry, as well as molecular simulation and electron microscopic analysis. Based on the understanding attained, the research group elucidated the nano-vesicle transformation mechanism of the 2D sheet structure, as described below. Initially, ammonium cations are exposed to the surface of the 2D structure. Deprotonation occurs spontaneously at the ammonium groups in order to reduce the electrostatic repulsion between the cations. The deprotonated neutral amine groups form hydrogen bonds with the neighboring ammonium groups, and this leads to a reversal of the intermolecular interaction from repulsion to attraction. The bending of the sheet material induced between the top layer and the bottom layer causes budding on the surface of the structure. The process is carried out gradually over time, and all the sheet structures disappear within one week, being spontaneously transformed into nano-vesicles. Interestingly, the results showed that the nano-vesicles generated can return to the 2D structure through the fusion of the vesicles under acidic conditions.

The new 2D sheet materials developed in the study are capable of spontaneously capturing various materials. Therefore, they will be applied as a next-generation drug delivery system and a nano-carrier for mRNA vaccines. In addition, the molecular interaction investigated in this study and the understanding of the molecular behavior can provide an important stepping stone for the R&D of new smart materials.

The results of the study, funded by the National Research Foundation of Korea (Basic Science Research Program and Basic Research Laboratory Program) and KU-KIST, were published online in Journal of the American Chemical Society, an authoritative journal in chemistry, on September 13, 2022.
* Article Title : Transformation of Supramolecular Membranes to Vesicles Driven by Spontaneous Gradual Deprotonation on Membrane Surfaces
* Journal: Journal of the American Chemical Society (2022년 9월 13일 online published; https://pubs.acs.org/doi/10.1021/jacs.2c06941)
* Authors: Seo Gun-hee (first author, KU), Kim Tae-yeon (coauthor, KU), Bowen Shen (coauthor, Fudan University), Kim Je-han (coauthor, POSTECH), and Kim Yong-ju (corresponding author, KU)

▲ A schematic illustration and a TEM image of the new 2D material that spontaneously transforms into nano-vesicles.