title: A model of localised Rac1 activation in endothelial cells due to fluid flow.
abstract: Endothelial cells respond to fluid flow by elongating in the direction of flow. Cytoskeletal changes and activation of signalling molecules have been extensively studied in this response, including: activation of receptors by mechano-transduction, actin filament alignment in the direction of flow, changes to cell-substratum adhesions, actin-driven lamellipodium extension, and localised activation of Rho GTPases. To study this process we model the force over a single cell and couple this to a model of the Rho GTPases, Rac and Rho, via a Kelvin-body model of mechano-transduction. It is demonstrated that a mechano-transducer can respond to the normal component of the force is likely to be a necessary component of the signalling network in order to establish polarity. Furthermore, the rate-limiting step of Rac1 activation is predicted to be conversion of Rac-GDP to Rac-GTP, rather than activation of upstream components. Modelling illustrates that the aligned endothelial cell morphology could attenuate the signalling network.
authors: Centre for Mathematics and Physics in the Life Sciences and Experimental Biology, University College London, Gower Street, London WC1E 7JE, United Kingdom. richard.allen@unc.edu
authors: R J
authors: RJ
authors: Allen
authors: I D L
authors: ID
authors: Bogle
authors: A J
authors: AJ
authors: Ridley
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D016764:Cell Polarity / Q000502:physiology; D042783:Endothelial Cells / Q000201:enzymology*; D004789:Enzyme Activation; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008954:Models, Biological; D011554:Pseudopodia / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: C107953:RAC1 protein, human; D020830:rac1 GTP-Binding Protein