Patterns of Mesenchymal Condensation in a Multiscale, Discrete Stochastic Model 英文参考文献.docVIP

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Patterns of Mesenchymal Condensation in a Multiscale, Discrete Stochastic Model 英文参考文献.doc

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Patterns of Mesenchymal Condensation in a Multiscale, Discrete Stochastic Model 英文参考文献

PatternsofMesenchymalCondensationina Multiscale,DiscreteStochasticModel Scott Christley1,2,Mark S.Alber2,3*,Stuart A.Newman4* 1DepartmentofComputerScience,UniversityofNotreDame,NotreDame,Indiana,UnitedStatesofAmerica,2InterdisciplinaryCenterfortheStudyofBiocomplexity, UniversityofNotreDame,NotreDame,Indiana,UnitedStatesofAmerica,3DepartmentofMathematics,UniversityofNotreDame,NotreDame,Indiana,UnitedStatesof America,4DepartmentofCellBiologyandAnatomy,NewYorkMedicalCollege,Valhalla,NewYork,UnitedStatesofAmerica Cellsoftheembryonicvertebratelimbinhigh-densitycultureundergochondrogenicpatternformation,whichresults intheproductionofregularlyspaced‘‘islands’’ofcartilagesimilartothecartilageprimordiaofthedevelopinglimb skeleton. The first step in this process, in vitro and in vivo, is the generation of ‘‘cell condensations,’’ in which the precartilage cells become more tightly packed at the sites at which cartilage will form. In this paper we describe a discrete, stochastic model for the behavior of limb bud precartilage mesenchymal cells in vitro. The model uses a biologicallymotivatedreaction–diffusionprocessandcell-matrixadhesion(haptotaxis)asthebasesofchondrogenic patternformation,wherebythebiochemicallydistinctcondensingcells,aswellasthesize,number,andarrangement of the multicellular condensations, are generated in a self-organizing fashion. Improving on an earlier lattice-gas representationofthesameprocess,itismultiscale(i.e.,cellandmoleculardynamicsoccurondistinctscales),andthe cellsarerepresentedasspatiallyextendedobjectsthatcanchangetheirshape.Theauthorscalibratethemodelusing experimental data and study sensitivity to changes in key parameters. The simulations have disclosed two distinct dynamicregimesforpatternself-organizationinvolvingtransientorstationaryinductivepatternsofmorphogens.The authors discuss these modes of pattern formation in relation to available experimental evidence for the in vitro system,aswellastheirimplicationsforunderstandinglimbskeletal