Insights into spheroids formation in cellulose nanofibrils and Matrigel hydrogels using AFM-based techniques

Roberta Teixeira Polez, Ngoc Huynh, Chris S. Pridgeon, Juan José Valle-Delgado, Riina Harjumäki*, Monika Österberg*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

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The recent FDA decision to eliminate animal testing requirements emphasises the role of cell models, such as spheroids, as regulatory test alternatives for investigations of cellular behaviour, drug responses, and disease modelling. The influence of environment on spheroid formation are incompletely understood, leading to uncertainty in matrix selection for scaffold-based 3D culture. This study uses atomic force microscopy-based techniques to quantify cell adhesion to Matrigel and cellulose nanofibrils (CNF), and cell-cell adhesion forces, and their role in spheroid formation of hepatocellular carcinoma (HepG2) and induced pluripotent stem cells (iPS(IMR90)-4). Results showed different cell behaviour in CNF and Matrigel cultures. Both cell lines formed compact spheroids in CNF but loose cell aggregates in Matrigel. Interestingly, the type of cell adhesion protein, and not the bond strength, appeared to be a key factor in the formation of compact spheroids. The gene expression of E- and N-cadherins, proteins on cell membrane responsible for cell-cell interactions, was increased in CNF culture, leading to formation of compact spheroids while Matrigel culture induced integrin-laminin binding and downregulated E-cadherin expression, resulting in looser cell aggregates. These findings enhance our understanding of cell-biomaterial interactions in 3D cultures and offer insights for improved 3D cell models, culture biomaterials, and applications in drug research.

Original languageEnglish
Article number101065
Number of pages13
JournalMaterials Today Bio
Early online date26 Apr 2024
Publication statusPublished - Jun 2024
MoE publication typeA1 Journal article-refereed


  • Atomic force microscopy
  • Cell adhesion molecules
  • Cell interactions
  • Cellulose nanofibrils
  • Matrigel
  • Spheroid formation


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