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Chemotaxis in Densely Populated Tissue Determines Germinal Center Anatomy and Cell Motility: A New Paradigm for the Development of Complex Tissues

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dc.contributor.authorHawkins, Jared B.en
dc.contributor.authorJones, Mark T.en
dc.contributor.authorPlassmann, Paul E.en
dc.contributor.authorThorley-Lawson, David A.en
dc.contributor.departmentElectrical and Computer Engineeringen
dc.date.accessioned2018-11-05T15:13:16Zen
dc.date.available2018-11-05T15:13:16Zen
dc.date.issued2011-12-01en
dc.description.abstractGerminal centers (GCs) are complex dynamic structures that form within lymph nodes as an essential process in the humoral immune response. They represent a paradigm for studying the regulation of cell movement in the development of complex anatomical structures. We have developed a simulation of a modified cyclic re-entry model of GC dynamics which successfully employs chemotaxis to recapitulate the anatomy of the primary follicle and the development of a mature GC, including correctly structured mantle, dark and light zones. We then show that correct single cell movement dynamics (including persistent random walk and inter-zonal crossing) arise from this simulation as purely emergent properties. The major insight of our study is that chemotaxis can only achieve this when constrained by the known biological properties that cells are incompressible, exist in a densely packed environment, and must therefore compete for space. It is this interplay of chemotaxis and competition for limited space that generates all the complex and biologically accurate behaviors described here. Thus, from a single simple mechanism that is well documented in the biological literature, we can explain both higher level structure and single cell movement behaviors. To our knowledge this is the first GC model that is able to recapitulate both correctly detailed anatomy and single cell movement. This mechanism may have wide application for modeling other biological systems where cells undergo complex patterns of movement to produce defined anatomical structures with sharp tissue boundaries.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0027650en
dc.identifier.eissn1932-6203en
dc.identifier.issue12en
dc.identifier.othere27650en
dc.identifier.pmid22145018en
dc.identifier.urihttp://hdl.handle.net/10919/85643en
dc.identifier.volume6en
dc.language.isoenen
dc.publisherPLOSen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleChemotaxis in Densely Populated Tissue Determines Germinal Center Anatomy and Cell Motility: A New Paradigm for the Development of Complex Tissuesen
dc.title.serialPLOS ONEen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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