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Science 324 (5924): 208-212

Copyright © 2009 by the American Association for the Advancement of Science

Multiscale Modeling of Form and Function

Adam J. Engler,1 Patrick O. Humbert,2 Bernhard Wehrle-Haller,3 Valerie M. Weaver4,5*

Abstract: Topobiology posits that morphogenesis is driven by differential adhesive interactions among heterogeneous cell populations. This paradigm has been revised to include force-dependent molecular switches, cell and tissue tension, and reciprocal interactions with the microenvironment. It is now appreciated that tissue development is executed through conserved decision-making modules that operate on multiple length scales from the molecular and subcellular level through to the cell and tissue level and that these regulatory mechanisms specify cell and tissue fate by modifying the context of cellular signaling and gene expression. Here, we discuss the origin of these decision-making modules and illustrate how emergent properties of adhesion-directed multicellular structures sculpt the tissue, promote its functionality, and maintain its homeostasis through spatial segregation and organization of anchored proteins and secreted factors and through emergent properties of tissues, including tension fields and energy optimization.

1 Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
2 Cell Cycle and Cancer Genetics Laboratory, Research Division, Peter MacCallum Cancer Center, Melbourne, Victoria, Australia.
3 Department of Cell Physiology and Metabolism, Centre Medical Universitaire, 1211 Geneva 4, Switzerland.
4 Center for Bioengineering and Tissue Regeneration and Department of Surgery, University of California, San Francisco (UCSF), San Francisco, CA 94143, USA.
5 Department of Anatomy, Department of Bioengineering and Therapeutic Sciences, Center for Regenerative Medicine and UCSF Comprehensive Cancer Center, San Francisco, CA 94143, USA.

* To whom correspondence should be addressed. E-mail: Valerie.weaver{at}

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