A Minimal Model of Signaling Network Elucidates Cell-to-Cell Stochastic Variability in Apoptosis 英文参考文献.docVIP
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A Minimal Model of Signaling Network Elucidates Cell-to-Cell Stochastic Variability in Apoptosis 英文参考文献
AMinimalModelofSignalingNetworkElucidates
Cell-to-CellStochasticVariabilityinApoptosis
SubhadipRaychaudhuri*
DepartmentofBiomedicalEngineering,BiophysicsGraduateGroup,GraduateGroupinImmunology,GraduateGroupinAppliedMathematics,UniversityofCalifornia
Davis,Davis,California,UnitedStatesofAmerica
Abstract
Background:Signalingnetworksaredesignedtosenseanenvironmentalstimulusandadapttoit.Weproposeandstudya
minimal model of signaling network that can sense and respond to external stimuli of varying strength in an adaptive
manner.Thestructureofthisminimalnetworkisderivedbasedonsomesimpleassumptionsonitsdifferentialresponseto
externalstimuli.
Methodology: We employ stochastic differential equations and probability distributions obtained from stochastic
simulationstocharacterizedifferentialsignalingresponseinourminimalnetworkmodel.Gillespie’sstochasticsimulation
algorithm(SSA)isusedinthisstudy.
Conclusions/Significance:Weshowthattheproposedminimalsignalingnetworkdisplaystwodistincttypesofresponseas
thestrengthofthestimulusisdecreased.Thesignalingnetworkhasadeterministicpartthatundergoesrapidactivationby
a strong stimulus in which case cell-to-cell fluctuations can be ignored. As the strength of the stimulus decreases, the
stochastic part of the network begins dominating the signaling response where slow activation is observed with
characteristic large cell-to-cell stochastic variability. Interestingly, this proposed stochastic signaling network can capture
some of the essential signaling behaviors of a complex apoptotic cell death signaling network that has been studied
through experiments and large-scale computer simulations. Thus we claim that the proposed signaling network is an
appropriate minimal model of apoptosis signaling. Elucidating the fundamental design principles of complex cellular
signalingpathwayssuchasapoptosis signalingremainsachallengingtask.Wedemonstratehowourproposedminimal
modelcanhelpelucidatetheeffectofaspecificapoptoticinhibitorBcl-2onapoptotics
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