loading page

Hyperosmolality in CHO Culture: Effects on cellular behavior and morphology
  • +3
  • Nadiya Romanova,
  • Tarek Niemann,
  • Johannes Greiner,
  • Barbara Kaltschmidt,
  • Christian Kaltschmidt,
  • Thomas Noll
Nadiya Romanova
Bielefeld University Faculty of Technology
Author Profile
Tarek Niemann
Bielefeld University Faculty of Biology
Author Profile
Johannes Greiner
Bielefeld University Faculty of Biology
Author Profile
Barbara Kaltschmidt
Bielefeld University Faculty of Biology
Author Profile
Christian Kaltschmidt
Bielefeld University Faculty of Biology
Author Profile
Thomas Noll
Bielefeld University Faculty of Technology
Author Profile

Abstract

Exposure of Chinese hamster ovary cells (CHO) to highly concentrated feed solution during fed-batch cultivation is known to result in an unphysiological osmolality increase (>300 mOsm/kg), affecting cell physiology and morphology. Extending previous observation on osmotic adaptation, the present study investigates for the first time potential effects of hyperosmolality on CHO cells on both population and single-cell level. We intentionally exposed CHO cells to hyperosmolality of up to 545 mOsm/kg during fed-batch cultivation. Contrarily to an expected osmosis effect promoting cell shrinkage, hyperosmolality-exposed CHO cells showed a nearly triplicated volume accompanied by ablation of proliferation. On the molecular level, we observed a strong hyperosmolality-dependent increase in mitochondrial activity in CHO cells compared to control. The companion article “Hyperosmolality in CHO Culture: Effects on Proteome” provides a proteome-based insight into the effects of hyperosmolality on mitochondria. In contrast to mitochondrial activity, hyperosmolality-dependent proliferation arrest of CHO cells was not accompanied by DNA accumulation or caspase-3/7-mediated apoptosis. Notably, we demonstrate for the first time a formation of up to eight multiple, small nuclei in single hyperosmolality-stressed CHO cells. The here presented observations reveal unknown hyperosmolality-dependent morphological changes and support existing data on the osmotic response in mammalian cells.

Peer review status:Published

12 Nov 2020Submitted to Biotechnology and Bioengineering
12 Nov 2020Submission Checks Completed
12 Nov 2020Assigned to Editor
16 Nov 2020Reviewer(s) Assigned
12 Jan 2021Review(s) Completed, Editorial Evaluation Pending
12 Jan 2021Editorial Decision: Revise Major
23 Feb 20211st Revision Received
23 Feb 2021Submission Checks Completed
23 Feb 2021Assigned to Editor
03 Mar 2021Reviewer(s) Assigned
08 Mar 2021Review(s) Completed, Editorial Evaluation Pending
08 Mar 2021Editorial Decision: Accept
27 Mar 2021Published in Biotechnology and Bioengineering. 10.1002/bit.27747