Papers by Author: Nobuhiko Yui

Abstract: The effect of molecular mobility of the supramolecular surfaces on the intracellular signaling pathway and the downstream cell functions were investigated. As a supramolecular cell culture platform, polyrotaxanes (PRXs) with a varied number of threaded host molecules were synthesized and coated on glass surfaces. As a result, mesenchymal stem cells (MSCs) adhering on the dynamic PRX surface shows down-regulated RhoA-associated signaling pathway resulting in narrow and protruded adhering morphology. Moreover, mouse induced pluripotent stem (iPS) cells on the dynamic PRX surface shows highly up-regulated Rac1-associated signaling pathway resulting in enhanced N-cadherin expression and cardiomyogenic differentiations. Because MSCs and iPS cells on the polymer surfaces with low molecular mobility show the reverse tendency with those of the dynamic PRX surfaces, it could be concluded that the control of molecular mobility induced by supramolecular PRXs is effective to control cytoskeletal signaling pathway and the downstream stem cell differentiation into the preference cells or tissue.

Abstract: Polyrotaxane-immobilized surfaces were prepared as a platform of dynamic surfaces, which can prevent from non-specific interaction with plasma proteins and platelet, and then modulate cellular functions via specific interaction with receptor protein-ligand binding through movable polyrotaxane backbone. The immobilization of the polyrotaxane was carried out via two-step protocol, in which the polyrotaxane with tetraethyleneglycol dodecanethiol (TEGDT) anchoring group at both terminals was fixed onto Au substrate via Au-S bond, followed by the fixation of TEGDT molecule onto the Au substrate to complete the loop formation of polyrotaxane on the Au substrate with the help of self-assembled monolayer formation of TEGDT. Their surface properties were characterized by means dynamic contact angle measurements, and preliminary studies as biomaterials were performed in terms of plasma protein adsorption onto their surfaces.

Abstract: The most definite feature in polyrotaxanes, in which many cyclic compounds are threaded onto a linear polymeric chains capped with bulky end-groups, is the mobility of cyclic compounds: these cyclic compounds may rotate and/or slide along the polymeric chain. Our previous studies have clarified that the mobility of ligands linked to the cyclic compounds is closely related to enhancing multivalent interaction with biological systems. This concept is now exploiting more practical applications for drug delivery such as gene delivery. We have designed biocleavable polyrotaxanes that have a necklace-like structure between many dimethylaminoethylcarbamoyl-α-cyclodextrins (DMAE-α-CDs) and a disulfide (SS)-introduced poly(ethylene glycol) (PEG) chain. The polyrotaxanes were found to show sufficient cleavage of S-S linkages under reducible condition, which led to triggering pDNA release via the dissociation of the non-covalent linkages between DMAE-α-CDs and the PEG chain. The polyrotaxanes were finally clarified to exhibit great transfection activity as well as non cytotoxicity.