Elastic free energy drives the shape of prevascular solid tumors

PLoS One. 2014 Jul 29;9(7):e103245. doi: 10.1371/journal.pone.0103245. eCollection 2014.

Abstract

It is well established that the mechanical environment influences cell functions in health and disease. Here, we address how the mechanical environment influences tumor growth, in particular, the shape of solid tumors. In an in vitro tumor model, which isolates mechanical interactions between cancer tumor cells and a hydrogel, we find that tumors grow as ellipsoids, resembling the same, oft-reported observation of in vivo tumors. Specifically, an oblate ellipsoidal tumor shape robustly occurs when the tumors grow in hydrogels that are stiffer than the tumors, but when they grow in more compliant hydrogels they remain closer to spherical in shape. Using large scale, nonlinear elasticity computations we show that the oblate ellipsoidal shape minimizes the elastic free energy of the tumor-hydrogel system. Having eliminated a number of other candidate explanations, we hypothesize that minimization of the elastic free energy is the reason for predominance of the experimentally observed ellipsoidal shape. This result may hold significance for explaining the shape progression of early solid tumors in vivo and is an important step in understanding the processes underlying solid tumor growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Cell Line, Tumor
  • Elasticity*
  • Humans
  • Models, Theoretical*
  • Neoplasms / pathology*
  • Stress, Mechanical
  • Tumor Burden

Grants and funding

This work was supported by an Alexander von Humboldt Postdoctoral Research Fellowship (KLM) and a Max Planck Society Postdoctoral Research Fellowship (KLM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.