Impact of Viscosity on Human Hepatoma Spheroids in Soft Core–Shell Microcapsules

Research output: Contribution to journalResearch articleContributedpeer-review


  • Xuan Peng - , University Cancer Centre, Helmholtz-Zentrum Dresden-Rossendorf (Author)
  • Željko Janićijević - , Helmholtz-Zentrum Dresden-Rossendorf (Author)
  • Sandy Lemm - , Chair of Bioinorganic and Radiopharmaceutical Chemistry, Helmholtz-Zentrum Dresden-Rossendorf (Author)
  • Sandra Hauser - , Helmholtz-Zentrum Dresden-Rossendorf (Author)
  • Michael Knobel - , Helmholtz-Zentrum Dresden-Rossendorf (Author)
  • Jens Pietzsch - , Helmholtz-Zentrum Dresden-Rossendorf, TUD Dresden University of Technology (Author)
  • Michael Bachmann - , National Center for Tumor Diseases (Partners: UKD, MFD, HZDR, DKFZ), Helmholtz-Zentrum Dresden-Rossendorf, German Cancer Research Center (DKFZ) (Author)
  • Larysa Baraban - , Helmholtz-Zentrum Dresden-Rossendorf (Author)


The extracellular environment regulates the structures and functions of cells, from the molecular to the tissue level. However, the underlying mechanisms influencing the organization and adaptation of cancer in three-dimensional (3D) environments are not yet fully understood. In this study, the influence of the viscosity of the environment is investigated on the mechanical adaptability of human hepatoma cell (HepG2) spheroids in vitro, using 3D microcapsule reactors formed with droplet-based microfluidics. To mimic the environment with different mechanical properties, HepG2 cells are encapsulated in alginate core–shell reservoirs (i.e., microcapsules) with different core viscosities tuned by incorporating carboxymethylcellulose. The significant changes in cell and spheroid distribution, proliferation, and cytoskeleton are observed and quantified. Importantly, changes in the expression and distribution of F-actin and keratin 8 indicate the relation between spheroid stiffness and viscosity of the surrounding medium. The increase of F-actin levels in the viscous medium can indicate an enhanced ability of tumor cells to traverse dense tissue. These results demonstrate the ability of cancer cells to dynamically adapt to the changes in extracellular viscosity, which is an important physical cue regulating tumor development, and thus of relevance in cancer biology.


Original languageEnglish
Article number2302609
JournalAdvanced healthcare materials
Issue number11
Publication statusPublished - 26 Apr 2024

External IDs

PubMed 38227977


Sustainable Development Goals


  • cell adaptation, cytoskeleton, hepatoma spheroids, hydrogel microcapsules, tumor microenvironment, Viscosity, Cell Proliferation, Actins/metabolism, Carcinoma, Hepatocellular/pathology, Humans, Alginates/chemistry, Hep G2 Cells, Liver Neoplasms/pathology, Spheroids, Cellular/metabolism, Capsules/chemistry, Cytoskeleton/metabolism