Autocatalytic Loop, Amplification and Diffusion A Mathematical and Computational Model of Cell Polarization in Neural Chemotaxis 英文参考文献.docVIP
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Autocatalytic Loop, Amplification and Diffusion A Mathematical and Computational Model of Cell Polarization in Neural Chemotaxis 英文参考文献
AutocatalyticLoop,AmplificationandDiffusion:A
MathematicalandComputationalModelofCell
PolarizationinNeuralChemotaxis
PaolaCausin*,GiuseppeFacchetti
DepartmentofMathematics‘‘F.Enriques’’,Universita` degliStudidiMilano,Milano,Italy
Abstract
Thechemotacticresponseofcellstogradedfieldsofchemicalcuesisacomplexprocessthatrequiresthecoordinationof
several intracellular activities. Fundamental steps to obtain a front vs. back differentiation in the cell are the localized
distribution of internal molecules and the amplification of the external signal. The goal of this work is to develop a
mathematicalandcomputationalmodelforthequantitativestudyofsuchphenomenainthecontextofaxonchemotactic
pathfindinginneuraldevelopment.Inordertoperformturningdecisions,axonsdevelopfront-backpolarizationintheir
distalstructure,thegrowthcone.Startingfromtherecentexperimentalfindingsofthebiasedredistributionofreceptorson
the growth cone membrane, driven by the interaction with the cytoskeleton, we propose a model to investigate the
significance ofthis process. Our maincontribution is toquantitatively demonstrate that theautocatalytic loop involving
receptors, cytoplasmicspecies andcytoskeletonisadequatetogiverise tothechemotacticbehaviorofneuralcells.We
assessthefactthatspatialbiasinreceptorsisaprecursorykeyeventforchemotacticresponse,establishingthenecessityof
atight linkbetween upstream gradient sensing and downstreamcytoskeleton dynamics.We analyze further crosslinked
effectsand,amongothers,thecontributiontopolarizationofinternalenzymaticreactions,whichentailtheproductionof
moleculeswithaone-to-morefactor.Themodelshowsthattheenzymaticefficiencyofsuchreactionsmustovercomea
thresholdinordertogiverisetoasufficientamplification,anotherfundamentalprecursorystepforobtainingpolarization.
Eventually,weaddressthecharacteristicbehavioroftheattraction/repulsionofaxonssubjectedtothesamecue,providing
aquantitativeindicatoroftheparameterswhichmorecriticallydeterminethisnontrivialchemotacticresponse.
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