P09-05

Over the Membrane: Study of Nucleic Acid Sequence Transfer Using Cholesterol-Modified DNA

Rinka AOKI *, Keita ABE, Satoshi MURATA, Hideaki MATSUBAYASHI, Shinichiro M NOMURA

Molecular Robotics Laboratory, Department of Robotics, Division of Mechanical Engineering,, Graduate School of Engineering, Tohoku University
( * E-mail: aoki.rinka.r6@dc.tohoku.ac.jp )

Molecular robotics is a pioneering engineering field that focuses on designing and constructing sensors, control circuits, and actuators at the molecular level, thereby enabling the development of robots that operate effectively on scales ranging from micrometers to nanometers. Specifically, DNA-based information-processing technologies are gaining attention as control circuits for molecular robots. However, because these systems operate in homogeneous aqueous solutions, effective compartmentalization is essential to maintain functional separation and targeted operation of these molecular systems. To this end, micrometer-sized lipid vesicles (liposomes) were used. Liposomes, which encapsulate water-soluble substances, are expected to function as the "body" of molecular robots, but the lipid membrane poses a challenge by hindering the passage of macromolecules, such as DNA, making communication with the external environment difficult.
Our laboratory's previous research[1] has shown that the hybridization of cholesterol-modified ssDNA enables the transmission of ssDNA with specific base sequences across membranes into liposomes. We refer to this mechanism as the "Chabashira" mechanism. In this study, we focused on optimizing the spatial arrangement of cholesterols within the membrane, leading to the development of a refined 'Chabashira.' Specifically, we tried to improve the system so that all sequences can be delivered across the membrane, rather than just the terminal sequences.
We evaluated its behavior on giant liposomes membrane by assessing the delivered DNAs by the system and their distribution, thereby confirming that molecular communication across the membrane was indeed achieved.
This mechanism is expected to increase the complexity of control circuits in nanodevices. Additionally, it has the potential to bring about new innovations in fields such as medicine and environmental monitoring, including drug delivery and environmental sensing.

[1] K. Yoshida, K. Abe, Y. Sato, I. Kawamata, R. J. Archer, H. T. Matsubayashi, S. Hamada, S. Murata, S. Nomura, ChemRxiv 2024, DOI 10.26434/chemrxiv-2024-571kp. This content is a preprint and has not been peer-reviewed.