The role of fluctuations and stress on the effective viscosity of cell aggregates

Proc Natl Acad Sci U S A. 2009 Oct 13;106(41):17271-5. doi: 10.1073/pnas.0902085106. Epub 2009 Sep 25.

Abstract

Cell aggregates are a tool for in vitro studies of morphogenesis, cancer invasion, and tissue engineering. They respond to mechanical forces as a complex rather than simple liquid. To change an aggregate's shape, cells have to overcome energy barriers. If cell shape fluctuations are active enough, the aggregate spontaneously relaxes stresses ("fluctuation-induced flow"). If not, changing the aggregate's shape requires a sufficiently large applied stress ("stress-induced flow"). To capture this distinction, we develop a mechanical model of aggregates based on their cellular structure. At stress lower than a characteristic stress tau*, the aggregate as a whole flows with an apparent viscosity eta*, and at higher stress it is a shear-thinning fluid. An increasing cell-cell tension results in a higher eta* (and thus a slower stress relaxation time t(c)). Our constitutive equation fits experiments of aggregate shape relaxation after compression or decompression in which irreversibility can be measured; we find t(c) of the order of 5 h for F9 cell lines. Predictions also match numerical simulations of cell geometry and fluctuations. We discuss the deviations from liquid behavior, the possible overestimation of surface tension in parallel-plate compression measurements, and the role of measurement duration.

MeSH terms

  • Animals
  • Biomechanical Phenomena / physiology
  • Cell Aggregation / physiology*
  • Cell Cycle / physiology
  • Cell Line, Tumor / cytology
  • Cell Line, Tumor / physiology
  • Cell Size
  • Cells / cytology*
  • Compressive Strength
  • Elasticity
  • Emulsions
  • Mice
  • Stress, Mechanical
  • Viscosity

Substances

  • Emulsions