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A complex systems approach to understand how cells control their shape and make cell fate decisions

Part 3. Proteomics

3.8. Systems Biology

Specialist Review

  1. Donald E. Ingber,
  2. Sui Huang

Published Online: 15 APR 2005

DOI: 10.1002/047001153X.g308208

Encyclopedia of Genetics, Genomics, Proteomics and Bioinformatics

Encyclopedia of Genetics, Genomics, Proteomics and Bioinformatics

How to Cite

Ingber, D. E. and Huang, S. 2005. A complex systems approach to understand how cells control their shape and make cell fate decisions. Encyclopedia of Genetics, Genomics, Proteomics and Bioinformatics. 3:3.8:114.

Author Information

  1. Harvard Medical School and Children's Hospital, Boston, MA, USA

Publication History

  1. Published Online: 15 APR 2005

Abstract

In this chapter, we analyze the mechanisms by which mammalian cells maintain their physical shape and make cell fate decisions whether to grow, move, differentiate, or die in response to chemical and physical signals during tissue development. We address how these robust and mutually exclusive, system-level behavioral programs emerge from the dynamics of molecular networks that establish both the hardware (structure) and the software (information processing) of the cell. Molecular filaments within the cytoskeleton self-organize using tensegrity architectural principles in which prestress and force balances between different filaments play key stabilizing roles. In this manner, the filaments form a physical network structure that stabilizes the shape of the cell while providing it with the flexibility necessary for movement. As for cellular information processing, genome-wide regulatory networks impose constraints on the collective dynamics of signaling molecules, so that the biochemical activity of genes and proteins exhibits large-scale coherent patterns that correspond to stable, high-dimensional attractor states. These attractors define distinct cell fates that are stable, yet can undergo regulated all-or-none transitions between distinct stable cell phenotypes. Because of the robustness of these attractors, physical cues devoid of molecular specificity, such as mechanical stress and cell shape distortion, can produce similar effects on cell behavior as highly specific growth factors. This coordination between structural networks and information networks is critical for the formation and homeostasis of complex tissue structures in multicellular organisms. Taken together, this work conveys the importance of complementing existing “bottom-up” approaches in systems biology that emphasize comprehensive characterization of molecular processes, with “top-down” approaches that place these molecular activities within the context of actual system-level properties at the level of the whole living cell.

Keywords:

  • tensegrity;
  • molecular networks;
  • attractor;
  • cell shape;
  • cell fate