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Ammonium Ion Effects on Hybridoma Cell Physiology


McQueen, Anne T. (1989) Ammonium Ion Effects on Hybridoma Cell Physiology. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/a159-dy39.


Ammonium ion is an important inhibitor of mammalian cell growth. Measurements of changes in hybridoma intracellular pH upon NH4Cl addition (using a flow cytometric assay in which cells are stained with a pH-sensitive fluorescent dye) indicate that NH+4 causes a steady-state cytoplasmic acidification. There is a correlation between NH4Cl effects on growth and on intracellular pH, and these effects are independent of the external pH value, suggesting that NH+4, not NH3 (produced by the dissociation of NH+4 at higher external pH values), is the species responsible for growth inhibition.

Ammonium ion has similar effects on batch growth in flasks in an incubator and in a bioreactor at controlled pH and dissolved oxygen concentration. Both decreases in the external pH value and increases in the NH4Cl concentration inhibit glucose consumption in batch growth. This is hypothesized to be due to intracellular pH decreases. However, cell growth is not dependent on glucose consumption. Changes in the external pH value and in the NH4Cl concentration, which result in growth inhibition, have no effect on the specific antibody production rate.

A mechanism is proposed and a mathematical model is developed to explain the intracellular pH decreases caused by NH+4. This model incorporates a detailed description of the behavior of the Na+/H+-exchanger, which is assumed to be the main pHi controller of the cell. The model is able to reproduce the salient features of the experimental results.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:Chemical engineering; biology
Degree Grantor:California Institute of Technology
Division:Chemistry and Chemical Engineering
Major Option:Chemical Engineering
Minor Option:Biology
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Bailey, James E.
Thesis Committee:
  • Bailey, James E. (chair)
  • Arnold, Frances Hamilton
  • Attardi, Giuseppe
  • Rothenberg, Ellen V.
Defense Date:26 May 1989
Additional Information:Page 65 missing from thesis file (PDF).
Record Number:CaltechETD:etd-02122007-131458
Persistent URL:
Related URLs:
URLURL TypeDescription adapted for Chapter 2.
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:614
Deposited By: Imported from ETD-db
Deposited On:06 Mar 2007
Last Modified:23 Aug 2021 19:31

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