A Model for the Increased Elastic Compliance in Human Cancer Cells
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A Model for the Increased Elastic Compliance in Human Cancer Cells Camilla Mohrdieck and Eduard Arzt Max Planck Institute for Metals Research Heisenbergstr. 3 70569 Stuttgart, Germany ABSTRACT Human epithelial cancer cells are known to exhibit a reorganization of their keratin cytoskeleton and an attendant change in their elastic stiffness upon incubation with a natural lipid. The change in the keratin network was modeled and the model structures were computationally deformed using a Finite Element Method. The simulation results show a marked difference in the mechanical behavior of the cells for tensile and compressive loading conditions. In the former case, the elastic compliance increases in agreement with experimental findings. We interpret this increase by applying principles of structural engineering and suggest that cells may generally use these principles to regulate their cytoskeletal architecture.
INTRODUCTION It has been demonstrated that incubation of human epithelial cancer cells with the natural, bioactive lipid sphingosylphosphorylcholine (SPC) induces a reorganization of the keratin cytoskeleton and an increase in the elastic compliance of these cells [1, 2]. Confocal microscopy of untreated control cells shows that the keratin cytoskeleton forms a homogeneous fiber network that is isotropically distributed around the nucleus [fig. 1]. After addition of 10µMol SPC, the micrographs depict the time dependent formation of densely spaced rings around the nucleus while the cytoskeletal region farther away from the nucleus is increasingly depleted of fibers [fig. 1]. This reorganization reaches a maximum after an incubation time of approximately 45min when the keratin network has become very inhomogeneous.
Figure 1. Immunofluorescence micrographs of human pancreatic cancer cells. The images show the reorganization of the keratin network as a function of the time after incubation of the cells with SPC. The scale bar represents 5µm. By courtesy of Beil et al., [1].
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In both studies the elastic stiffness of untreated and incubated cells was measured by periodically deforming the cells between two micro-plates. The results agree very well and show that for tensile loading conditions the effect of SPC is to reduce the elastic stiffness by a factor of 2-3 while the amount of dissipated energy is enhanced with respect to the control cells. This effect of SPC has been shown to be independent of the arrangement of other cytoskeletal fibers such as actin and microtubules. In [2] the cells were also periodically contracted, which did not result in a significant change of the elastic stiffness. The objective of this study is to see if the observed mechanical behavior of the cancer cells can be explained by the SPC-induced reorganization of the keratin network. To this end, we have constructed model cells representing the cancer cells at different stages of incubation with SPC. The model cells were deformed in a computer simulation by applying the Finite Element Method (FEM), and the evaluated elasti
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