Endothelial Cell Capture of Heparin-Binding Growth Factors under Flow

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dc.contributor.authorZhao, Bingen
dc.contributor.authorZhang, Changjiangen
dc.contributor.authorForsten-Williams, Kimberlyen
dc.contributor.authorZhang, Junen
dc.contributor.authorFannon, Michaelen
dc.contributor.departmentChemical Engineeringen
dc.date.accessioned2018-11-19T18:38:15Zen
dc.date.available2018-11-19T18:38:15Zen
dc.date.issued2010-10en
dc.description.abstractCirculation is an important delivery method for both natural and synthetic molecules, but microenvironment interactions, regulated by endothelial cells and critical to the molecule's fate, are difficult to interpret using traditional approaches. In this work, we analyzed and predicted growth factor capture under flow using computer modeling and a three-dimensional experimental approach that includes pertinent circulation characteristics such as pulsatile flow, competing binding interactions, and limited bioavailability. An understanding of the controlling features of this process was desired. The experimental module consisted of a bioreactor with synthetic endothelial-lined hollow fibers under flow. The physical design of the system was incorporated into the model parameters. The heparin-binding growth factor fibroblast growth factor-2 (FGF-2) was used for both the experiments and simulations. Our computational model was composed of three parts: (1) media flow equations, (2) mass transport equations and (3) cell surface reaction equations. The model is based on the flow and reactions within a single hollow fiber and was scaled linearly by the total number of fibers for comparison with experimental results. Our model predicted, and experiments confirmed, that removal of heparan sulfate (HS) from the system would result in a dramatic loss of binding by heparin-binding proteins, but not by proteins that do not bind heparin. The model further predicted a significant loss of bound protein at flow rates only slightly higher than average capillary flow rates, corroborated experimentally, suggesting that the probability of capture in a single pass at high flow rates is extremely low. Several other key parameters were investigated with the coupling between receptors and proteoglycans shown to have a critical impact on successful capture. The combined system offers opportunities to examine circulation capture in a straightforward quantitative manner that should prove advantageous for biologicals or drug delivery investigations.en
dc.description.sponsorshipThis study was supported by NIH under grant HL086644, and by a Research to Prevent Blindness Challenge Grant. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1371/journal.pcbi.1000971en
dc.identifier.eissn1553-7358en
dc.identifier.issn1553-734Xen
dc.identifier.issue10en
dc.identifier.othere1000971en
dc.identifier.pmid21060855en
dc.identifier.urihttp://hdl.handle.net/10919/85911en
dc.identifier.volume6en
dc.language.isoen_USen
dc.publisherPLOSen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectsmooth-muscle-cellsen
dc.subjectbarrier in-vitroen
dc.subjectfibroblast-growthen
dc.subjectsulfate proteoglycansen
dc.subjectsignal-transductionen
dc.subjectangiogenic factorsen
dc.subjectbfgf bindingen
dc.subjectmodelen
dc.subjectreceptorsen
dc.subjectfgfen
dc.titleEndothelial Cell Capture of Heparin-Binding Growth Factors under Flowen
dc.title.serialPLOS Computational Biologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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