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Published August 1, 2000 | public
Journal Article Open

Bioengineering models of cell signaling

Abstract

Strategies for rationally manipulating cell behavior in cell-based technologies and molecular therapeutics and understanding effects of environmental agents on physiological systems may be derived from a mechanistic understanding of underlying signaling mechanisms that regulate cell functions. Three crucial attributes of signal transduction necessitate modeling approaches for analyzing these systems: an ever-expanding plethora of signaling molecules and interactions, a highly interconnected biochemical scheme, and concurrent biophysical regulation. Because signal flow is tightly regulated with positive and negative feedbacks and is bidirectional with commands traveling both from outside-in and inside-out, dynamic models that couple biophysical and biochemical elements are required to consider information processing both during transient and steady-state conditions. Unique mathematical frameworks will be needed to obtain an integrated perspective on these complex systems, which operate over wide length and time scales. These may involve a two-level hierarchical approach wherein the overall signaling network is modeled in terms of effective "circuit" or "algorithm" modules, and then each module is correspondingly modeled with more detailed incorporation of its actual underlying biochemical/biophysical molecular interactions.

Additional Information

"Reprinted, with permission, from the Annual Review of Biomedical Engineering, Volume 2 copyright 2000 by Annual Reviews, www.annualreviews.org" We thank Adam Arkin for helpful suggestions and valuable critique of our manuscript. This work was funded by the NIH Biotechnology Training Grant at MIT and an Anna Fuller Graduate Fellowship in Molecular Oncology from MIT Cancer Research Center to ARA, and NIH grant NIGMS 53905 and NSF grant BES 9727146 to DAL.

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August 21, 2023
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