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1、HHSPublicAccessAuthormanuscriptAuthorManuscriptAuthorManuscriptCell.Authormanuscript;availableinPMC2017June02.AuthorManuscriptAuthorManuscriptPublishedinfinaleditedformas:Cell.2016June2;165(6):1479–1492.doi:10.1016/j.cell.2016.05.045.RelativeRatesofS
2、urfaceandVolumeSynthesisSetBacterialCellSizeLeighK.HarrisandJulieA.TheriotBiophysicsProgram,DepartmentofBiochemistry,andHowardHughesMedicalInstitute,StanfordUniversity,Stanford,CA94305,USASummaryManystudieshavefocusedonthemechanismsunderlyinglengthan
3、dwidthdeterminationinrod-shapedbacteria.Here,wefocusinsteadoncellsurfaceareatovolumeratio(SA/V),anddemonstratethatSA/Vhomeostasisunderliessizedetermination.Weproposeamodelwherebytheinstantaneousratesofsurfaceandvolumesynthesisbothscalewithvolume.This
4、modelpredictsthattheserelativeratesdictateSA/Vandthatcellsapproachanewsteady-stateSA/Vexponentially,withadecayconstantequaltothevolumegrowthrate.Totestthis,weexposeddiversebacterialspeciestosublethalconcentrationsofacellwallbiosynthesisinhibitorandob
5、serveddose-dependentdecreasesinSA/V.Furthermore,thisdecreasewasexponentialandhadtheexpecteddecayconstant.ThemodelalsoquantitativelydescribesSA/Valterationsinducedbyotherchemical,nutritional,andgeneticperturbations.Weadditionallypresentevidenceforasur
6、facematerialaccumulationthresholdunderlyingdivision,sensitizingcelllengthtochangesinSA/Vrequirements.IntroductionGeneticallyidenticalrod-shapedbacterialcellsadoptaremarkablynarrowrangeoflengthsandwidthsunderconstantgrowthconditions(Schaechteretal.,19
7、62).However,rapidlygrowingcellsinnutrient-richmediumaretypicallymuchlarger,bothinwidthandlength,thanisogeniccellsgrowingslowlyinminimalmedium(Schaechteretal.,1958).Theseclassicobservationsraisequestionsthatremainopenandwhoseanswerswillbecriticalforat
8、horoughunderstandingofbacterialphysiology:whatprinciplessetandmaintainthisnarrowrangeofcellulardimensions,andhowarethesedimensionsmodulatedinresponsetoachangeintheenvironment?Inmostbacteria,thecellwallplaysadeterministicroleinsettingthesizeandshapeof