Simulating Properties of In Vitro Epithelial Cell Morphogenesis 英文参考文献.docVIP

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Simulating Properties of In Vitro Epithelial Cell Morphogenesis 英文参考文献.doc

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Simulating Properties of In Vitro Epithelial Cell Morphogenesis 英文参考文献

SimulatingPropertiesofInVitroEpithelial CellMorphogenesis Mark R.Grant1,Keith E.Mostov2,Thea D.Tlsty3,C.Anthony Hunt1,4* 1UniversityofCaliforniaSanFrancisco/UniversityofCaliforniaBerkeleyJointGraduateGroupinBioengineering,UniversityofCaliforniaBerkeley,Berkeley,California,United States of America, 2 Department of Anatomy, University of California San Francisco, San Francisco, California, United States of America, 3 Department of Pathology, University of California San Francisco, San Francisco, California, United States of America, 4 Department of Biopharmaceutical Sciences, Biosystems Group, University of CaliforniaSanFrancisco,SanFrancisco,California,UnitedStatesofAmerica Howdoindividualepithelialcells(ECs)organizeintomulticellularstructures?ECsarestudiedinvitrotohelpanswer that question. Characteristic growth features include stable cyst formation in embedded culture, inverted cyst formationinsuspensionculture,andlumenformationinoverlayculture.Formationofthesecharacteristicstructuresis believedtobeaconsequenceofanintrinsicprogramofdifferentiationandde-differentiation.Tohelpdiscoverhow such aprogram mayfunction, we developed an in silico analogue in which space, events, and time arediscretized. Software agents and objects represent cells and components of the environment. ‘‘Cells’’ act independently. The ‘‘program’’ governing their behavior is embedded within each in the form of axioms and an inflexible decisional process.Relationships between theaxioms and recognized cell functions arespecified. Interactions between ‘‘cells’’ andenvironmentcomponentsduringsimulationgiverisetoacomplexinsilicophenotypecharacterizedbycontext- dependentstructuresthatmimiccounterpartsobservedinfourdifferentinvitrocultureconditions:atargetedsetofin vitro phenotypic attributes was matched by in silico attributes. However, for a particular growth condition, the analoguefailedtoexhibitbehaviorscharacteristicoffunctionallypolarizedECs.Wesolvedthisproblembyfollowing an iterative refinem