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Elastic free energy drives the shape of prevascular solid tumors.

Mills KL, Kemkemer R, Rudraraju S, Garikipati K - PLoS ONE (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of New Materials and Biosystems, Max Planck Institute for Intelligent Systems, Stuttgart, Germany.

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.

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3D rendering of an oblate ellipsoidal tumor.The 3D rendering, created using images taken with a light sheet fluorescence microscope, is rotated about the vertical axis in this sequence of images. Blue: Hoechst-stained nuclei; Red: E-cadherin. Scale bar is 90 µm.
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pone-0103245-g001: 3D rendering of an oblate ellipsoidal tumor.The 3D rendering, created using images taken with a light sheet fluorescence microscope, is rotated about the vertical axis in this sequence of images. Blue: Hoechst-stained nuclei; Red: E-cadherin. Scale bar is 90 µm.

Mentions: Light sheet fluorescence microscope imaging (for Figure 1) was performed on a Zeiss Lightsheet Z.1 microscope with the help of Dr. C. Schwindling at the Zeiss Microscopy Labs in Munich, Germany and (for Figure 2) on a custom-built light sheet fluorescence microscope in the lab of Prof. H. Schneckenburger with the assistance of S. Schickinger at the University of Aalen, Germany [20].


Elastic free energy drives the shape of prevascular solid tumors.

Mills KL, Kemkemer R, Rudraraju S, Garikipati K - PLoS ONE (2014)

3D rendering of an oblate ellipsoidal tumor.The 3D rendering, created using images taken with a light sheet fluorescence microscope, is rotated about the vertical axis in this sequence of images. Blue: Hoechst-stained nuclei; Red: E-cadherin. Scale bar is 90 µm.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4114546&req=5

pone-0103245-g001: 3D rendering of an oblate ellipsoidal tumor.The 3D rendering, created using images taken with a light sheet fluorescence microscope, is rotated about the vertical axis in this sequence of images. Blue: Hoechst-stained nuclei; Red: E-cadherin. Scale bar is 90 µm.
Mentions: Light sheet fluorescence microscope imaging (for Figure 1) was performed on a Zeiss Lightsheet Z.1 microscope with the help of Dr. C. Schwindling at the Zeiss Microscopy Labs in Munich, Germany and (for Figure 2) on a custom-built light sheet fluorescence microscope in the lab of Prof. H. Schneckenburger with the assistance of S. Schickinger at the University of Aalen, Germany [20].

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of New Materials and Biosystems, Max Planck Institute for Intelligent Systems, Stuttgart, Germany.

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.

Show MeSH
Related in: MedlinePlus