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Engineering Three-Dimensional Cellular Organization by Regulating Bound Water-Mediated Cell-Substrate Interactions
Michiharu Kawahara1, Kotomu Miyazaki1, Takahisa Anada1,2
1Department of Applied Chemistry, Graduate School of Engineering, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan.
ACS Omega
|November 24, 2025
Summary
Researchers enhanced 3D organoid engineering by controlling hydrated water content in polymer coatings. This method promotes 3D cell adhesion and enables new disease models for drug screening.
Area of Science:
- Biomaterials Science
- Tissue Engineering
- Cell Biology
Background:
- Organoid culture technologies are advancing for biomimetic models.
- Reproducible construction of complex organoid architectures using synthetic polymers is challenging.
- Controlling cell-substrate interactions is vital for regulating 3D cell adhesion.
Purpose of the Study:
- To investigate if increasing hydrated water content of poly-(2-methoxyethyl acrylate) (PMEA) derivatives can induce a transition from 2D to 3D cell adhesion.
- To develop novel synthetic polymer substrates for advanced organoid engineering and disease modeling.
Main Methods:
- Synthesized PMEA derivative block copolymers with varying ethylene glycol (EG) side-chain lengths.
- Utilized atomic force microscopy-based single-cell force spectroscopy to quantify cell-substrate interactions.
- Established an in vitro model of metabolic dysfunction-associated steatohepatitis (MASH).
Main Results:
- Increased bound water content on polymer surfaces weakened cell-substrate interactions.
- This weakening promoted cell-cell interactions and facilitated 3D cell adhesion.
- The developed polymer substrates successfully modeled MASH, showing lipid accumulation and inflammatory cytokine expression.
Conclusions:
- Modulating hydrated water content of polymer coatings offers a novel strategy for guiding 3D cellular organization.
- PMEA derivatives are promising materials for 3D organoid engineering and disease modeling platforms.
- The MASH model demonstrates utility for drug screening applications.
