Morphology, geometry and mechanical properties of GAP A3 hybridoma cells as a function of the cell cycle

The sensitivity of animal cells in bioreactor culture to hydrodynamic shear and abrasion results in reduced cell growth rate and viability and is widely perceived as a barrier to scale-up in processing. Cell shear- and abrasion-sensitivity is also important in determining the behavior of proliferating cells in other hydrodynamic environments such as metastasizing cancer cells in the blood stream. Little is known about the link between morphology, structure and mechanical properties of a given cell line, especially with respect to variations throughout the cell cycle. In our experiments, distinct hybridoma cell morphologies were identified and correlated with phases of the cell cycle by video microscopic observation of synchronized cells, and of individual cells that were followed throughout their cell cycle. Micropipet manipulation was used to measure the geometrical (cell volume) and mechanical (apparent cell viscosity) properties of single cells. As the cell cycle progressed, an increase in cell volume from 1400 μm3 to 5700 μm3 was accompanied by an increase in apparent cell viscosity from 430 poise to 12,000 poise, consistent with an accumulation of more cytoplasmic material in the older cells. Hybridomas are representative of the various leukemias derived from hemopoietic cells and even though they appeared to be rather shear-insensitive, the wide range of property values demonstrates that a given cell line cannot be characterized by a single value for any one property, and that properties must be related to the cell cycle when considering proliferating cells. Identifying such cell cycle dependent features in metastasizing cancer cells could lead to clinical treatments directed at making them more shear- and abrasion-sensitive and therefore more likely to be killed by the natural hydrodynamic forces of the circulatory system.

Duke Scholars

Author David Needham Thomas Lord Department of Mechanical Engineering and Materia ...