Autologous Gradient Formation under Differential Interstitial Fluid Flow Environments

dc.contributor.authorStine, Caleb A.en
dc.contributor.authorMunson, Jennifer M.en
dc.date.accessioned2022-01-11T13:49:13Zen
dc.date.available2022-01-11T13:49:13Zen
dc.date.issued2022-01-04en
dc.date.updated2022-01-10T14:38:22Zen
dc.description.abstractFluid flow and chemokine gradients play a large part in not only regulating homeostatic processes in the brain, but also in pathologic conditions by directing cell migration. Tumor cells in particular are superior at invading into the brain resulting in tumor recurrence. One mechanism that governs cellular invasion is autologous chemotaxis, whereby pericellular chemokine gradients form due to interstitial fluid flow (IFF) leading cells to migrate up the gradient. Glioma cells have been shown to specifically use CXCL12 to increase their invasion under heightened interstitial flow. Computational modeling of this gradient offers better insight into the extent of its development around single cells, yet very few conditions have been modelled. In this paper, a computational model is developed to investigate how a CXCL12 gradient may form around a tumor cell and what conditions are necessary to affect its formation. Through finite element analysis using COMSOL and coupled convection-diffusion/mass transport equations, we show that velocity (IFF magnitude) has the largest parametric effect on gradient formation, multidirectional fluid flow causes gradient formation in the direction of the resultant which is governed by IFF magnitude, common treatments and flow patterns have a spatiotemporal effect on pericellular gradients, exogenous background concentrations can abrogate the autologous effect depending on how close the cell is to the source, that there is a minimum distance away from the tumor border required for a single cell to establish an autologous gradient, and finally that the development of a gradient formation is highly dependent on specific cell morphology.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationStine, C.A.; Munson, J.M. Autologous Gradient Formation under Differential Interstitial Fluid Flow Environments. Biophysica 2022, 2, 16-33.en
dc.identifier.doihttps://doi.org/10.3390/biophysica2010003en
dc.identifier.urihttp://hdl.handle.net/10919/107534en
dc.language.isoenen
dc.publisherMDPIen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectinterstitial flowen
dc.subjectgliomaen
dc.subjectchemotaxisen
dc.subjectautologousen
dc.subjectcomputationalen
dc.subjectgradienten
dc.subjectCXCL12en
dc.subjectmigrationen
dc.titleAutologous Gradient Formation under Differential Interstitial Fluid Flow Environmentsen
dc.title.serialBiophysicaen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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