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Conceptual and Experimental Tools to Understand Spatial Effects and Transport Phenomena in Nonlinear Biochemical Networks Illustrated with Patchy Switching

Pompano, Rebecca R. and Chiang, Andrew H. and Kastrup, Christian J. and Ismagilov, Rustem F. (2017) Conceptual and Experimental Tools to Understand Spatial Effects and Transport Phenomena in Nonlinear Biochemical Networks Illustrated with Patchy Switching. Annual Review of Biochemistry, 86 . pp. 333-356. ISSN 0066-4154. doi:10.1146/annurev-biochem-060815-014207.

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Many biochemical systems are spatially heterogeneous and exhibit nonlinear behaviors, such as state switching in response to small changes in the local concentration of diffusible molecules. Systems as varied as blood clotting, intracellular calcium signaling, and tissue inflammation are all heavily influenced by the balance of rates of reaction and mass transport phenomena including flow and diffusion. Transport of signaling molecules is also affected by geometry and chemoselective confinement via matrix binding. In this review, we use a phenomenon referred to as patchy switching to illustrate the interplay of nonlinearities, transport phenomena, and spatial effects. Patchy switching describes a change in the state of a network when the local concentration of a diffusible molecule surpasses a critical threshold. Using patchy switching as an example, we describe conceptual tools from nonlinear dynamics and chemical engineering that make testable predictions and provide a unifying description of the myriad possible experimental observations. We describe experimental microfluidic and biochemical tools emerging to test conceptual predictions by controlling transport phenomena and spatial distribution of diffusible signals, and we highlight the unmet need for in vivo tools.

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Ismagilov, Rustem F.0000-0002-3680-4399
Additional Information:© 2017 Annual Reviews. This work was supported in part by a National Institutes of Health Director's Pioneer Award (DP10D003584, R.F.I.), a Jacobs Institute for Molecular Engineering for Medicine Award (R.F.I.), a National Science Foundation Emerging Frontiers in Research and Innovation Award (1137089, R.F.I.), an Individual Biomedical Research Award from The Hartwell Foundation (R.R.P.), and a Canadian Institutes of Health Research Award (MSH-130166, C.J.K.). We thank Natasha Shelby for contributions to writing and editing this manuscript. The authors are not aware of any affiliations, memberships, funding, or financial holdings that might be perceived as affecting the objectivity of this review.
Group:Jacobs Institute for Molecular Engineering for Medicine
Funding AgencyGrant Number
Jacobs Institute for Molecular Engineering for MedicineUNSPECIFIED
Hartwell FoundationUNSPECIFIED
Canadian Institutes of HealthMSH-130166
Subject Keywords:state switching, signaling, flow, mass transfer, Damköhler number, microfluidics
Record Number:CaltechAUTHORS:20170628-083437438
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:78633
Deposited By: Tony Diaz
Deposited On:28 Jun 2017 16:44
Last Modified:15 Nov 2021 17:41

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