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Biophys. J. BioFAST: First Published March 24, 2006. doi:10.1529/biophysj.105.073494
© 2006 by the Biophysical Society.

A more recent version of this article appeared on June 15, 2006.
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BIOPHYSICAL THEORY AND MODELING

3D Modeling of Mechanical Forces in the Extra-cellular Matrix during Epithelial Lumen Formation

Dehong Zeng 1, Aldo Ferrari 2, Jens Ulmer 3, Alexey Veligodskiy 2, Peter Fischer 2, Joachim Spatz 3, Yiannis Ventikos 4, Dimos Poulikakos 2* and Ruth Kroschewski 2

1 Swiss Federal Institute of Techonlogy
2 Swiss Federal Institute of Technology
3 University of Heidelberg
4 University of Oxford

* To whom correspondence should be addressed. E-mail: dimos.poulikakos{at}ltnt.iet.mavt.ethz.ch.

Submitted on August 29, 2005
Revised on November 5, 2005
Accepted on 3 March 2006


  Abstract
Mechanical interactions between cells and extra-cellular matrix (ECM) mediate epithelial cyst formation. This work relies on the combination of numerical modeling with live cell imaging, to piece together a novel non-intrusive method for determining 3D mechanical forces caused by shape changes of a multi-cellular aggregate at the early stages of epithelial cyst formation. We analyzed the evolution of Madin-Darby Canine Kidney (MDCK) cells in three-dimensional (3D) cultures using time-lapse microscopy, with type I collagen gel forming the ECM. The evolving 3D interface between the ECM and the cell aggregate was obtained from microscopy images, and the stress on the surface of a proliferating aggregate and in the surrounding ECM was calculated using the finite element method (FEM). The viscoelastic properties of the ECM (a needed input for the FEM solver) were obtained through oscillatory shear flow experiments on a rheometer. For validation purpose, the forces exerted by an aggregate on a force-sensor array were measured and compared against the computational results.

Key Words: 3D mechanical forces, finite element model, force-sensor array, morphogenesis, time-lapse microscopy




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A. Ferrari, A. Veligodskiy, U. Berge, M. S. Lucas, and R. Kroschewski
ROCK-mediated contractility, tight junctions and channels contribute to the conversion of a preapical patch into apical surface during isochoric lumen initiation
J. Cell Sci., November 1, 2008; 121(21): 3649 - 3663.
[Abstract] [Full Text] [PDF]


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Copyright © 2006 by the Biophysical Society.