# High-Quality Three-Dimensionally Cultured Cells Using Interfaces of Diblock Copolymers Containing Different Ratios of Zwitterionic N‑Oxides https://mdr.nims.go.jp/datasets/a50ed7f9-479c-4db2-b551-dcc36b63cc2a ## File - [240815_manuscript_revise_highlight.docx](https://mdr.nims.go.jp/filesets/9d25d785-71f5-4f96-a5f7-944cad131713/download) ([Detail](https://mdr.nims.go.jp/filesets/9d25d785-71f5-4f96-a5f7-944cad131713.md)) - [240815_SI_revise_highlight (1).docx](https://mdr.nims.go.jp/filesets/29ca8d52-32d4-426b-8754-0714f84f6f2b/download) ([Detail](https://mdr.nims.go.jp/filesets/29ca8d52-32d4-426b-8754-0714f84f6f2b.md)) ## Id a50ed7f9-479c-4db2-b551-dcc36b63cc2a ## Local identifier ## Visibility open_to_public ## State published ## Created at 2024-10-09T05:40:57.901829Z ## Updated at 2025-08-18T23:30:21.299365Z ## Published at 2025-08-18T23:20:12.305150Z ## Doi https://doi.org/10.48505/nims.4830 ## First published url https://doi.org/10.1021/acsami.4c10118 ## Date published 2024-08-28 ## Recorded date published 2024-8-28 ## Resource type journal_article ## Manuscript type accepted_manuscript ## Collection ## Title - title: High-Quality Three-Dimensionally Cultured Cells Using Interfaces of Diblock Copolymers Containing Different Ratios of Zwitterionic N‑Oxides title_type: alternative lang: ja - title: High-Quality Three-Dimensionally Cultured Cells Using Interfaces of Diblock Copolymers Containing Different Ratios of Zwitterionic N‑Oxides title_type: original lang: en ## Description - description: To control three-dimensional (3D) cell spheroid formation, it is well-known the surface physicochemical and mechanical properties of cell culture materials are important; however, the formation and function of 3D cells are still unclear. This study demonstrated the precise control of the formation of 3D cells and 3D cell functions using diblock copolymers containing different ratios of a zwitterionic trimethylamine N-oxide group. The diblock copolymers were composed of poly(n-butyl methacrylate) (PBMA) as the hydrophobic unit for surface coating on a cell culture dish and stabilization in water, and poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) as the precursor of N-oxide. The zwitterionic N-oxide converted from 0 to 100% using PDMAEMA. The wettability and surface zeta potential varied with different ratios of N-oxide diblock copolymercoated surfaces, and the amount of protein adsorbed in the cell culture medium decreased monotonically with increasing N-oxide ratio. 3D cell spheroid formations were observed by seeding human umbilical cord mesenchymal stem cells (hUC-MSCs) in diblock copolymer-coated flat-bottom well plates, and the N-oxide ratio was over 40%. The cells proliferated in two-dimensions (2D) and did not form spheroids when the N-oxide ratio was less than 20%. Interestingly, the expression of undifferentiated markers of hUC-MSCs was higher on surfaces that adsorbed proteins to some extent and formed 50−150 μm spheroids in the range of 40−70% of N-oxide ratio. We revealed that a moderately protein-adsorbed surface allows precise control of spheroid formation and undifferentiated 3D cells and has potential applications for high-quality spheroids in regenerative medicine and drug screening. description_type: abstract lang: eng ## Creator - name: Naoto Ogiwara role: author organization: Department of Bioengineering, School of Engineering, The University of Tokyo - name: Takenobu Nakano role: author organization: Biotech Business Unit, Incubation Center, artience Co., Ltd. - name: Koki Baba role: author organization: Biotech Business Unit, Incubation Center, artience Co., Ltd. - name: Hidenori Noguchi role: author orcid: https://orcid.org/0000-0001-9643-1689 organization: National Institute for Materials Science department: Research Center for Energy and Environmental Materials (GREEN)/Battery and Cell Materials Field/Interface Electrochemistry Group ror: https://ror.org/026v1ze26 - name: Tsukuru Masuda role: author organization: Department of Bioengineering, School of Engineering, The University of Tokyo - name: Madoka Takai role: author organization: Department of Bioengineering, School of Engineering, The University of Tokyo ## Contact agent ## Publisher organization: American Chemical Society (ACS) ## Managing organization ## Keyword - subject: cell spheroid schema: not_defined - subject: N-oxide, diblock copolymer schema: not_defined - subject: protein adsorption schema: not_defined - subject: atomic force microscope schema: not_defined - subject: sum frequency generation schema: not_defined ## Rights - description: This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Applied Materials & Interfaces, copyright © 2024 The Authors, published by American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acsami.4c10118 identifier: http://rightsstatements.org/vocab/InC/1.0/ ## Other identifier(s) ## Data origin - data_origin_type: other ## Embargo start_date: 2024-08-19 end_date: 2025-08-19 ## Journal - title: ACS Applied Materials & Interfaces issn: '19448244' volume: '16' issue: '34' ## Conference ## Related item ## Funding - identifier: 20H02795 funder_name: Japan Society for the Promotion of Science - identifier: 21H05231 funder_name: Japan Society for the Promotion of Science ## Instrument ## Instrument operator ## Instrument managing organization ## Measurement method ## Specimen ## Chemical composition ## Structure for specimen ## Structural feature for specimen ## Specific property for specimen ## Process for specimen treatment ## Computational method ## Energy level/transition state ## Software ## Custom property ## Fileset - id: 9d25d785-71f5-4f96-a5f7-944cad131713 filename: 240815_manuscript_revise_highlight.docx content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document size: 5657577 md5: 746e9d002cf2845e0fc231855cbee5ed - id: 29ca8d52-32d4-426b-8754-0714f84f6f2b filename: 240815_SI_revise_highlight (1).docx content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document size: 7192268 md5: d98de4b9ad2b912d3d40728c5cd15ed0 ## Thumbnail fileset_id: 29ca8d52-32d4-426b-8754-0714f84f6f2b filename: 240815_SI_revise_highlight (1).docx