Technical Advance: Introducing a novel metric, directionality time, to quantify human neutrophil chemotaxis as a function of matrix composition and stiffness

[摘要] Adirectconsequenceofcellularmovementandnavigation,migrationincorporateselementsofspeed,direction,andpersistenceofmotion.CurrenttechniquestoparameterizethetrajectoryofachemotaxingcellmostcommonlypairmigrationspeedwithsomemeasureofpersistencebycalculatingMSD,RMSspeed,TAD,and/orCI.WeaddressinherentlimitationsinTADandCIforcomparativeanalysisbyintroducingtwonewanalyticaltoolstoquantifypersistence:directionalityindexanddirectionalitytime.Withtheuseofthesetools,weshowthatthemechanicalpropertiesoftheunderlyingsubstratecontributesignificantlytotheregulationofhumanneutrophilchemotaxistowardfMLPonFgn‐,Col‐,andFn‐coatedgelsofvaryingelasticity.Theβ1‐integrinligandColdemonstratedmechanosensitivespeed.Incontrast,β2‐integrinligandFgnsupportedmechanosensitivepersistence.Fn,recognizedbyβ1andβ2integrins,mechanoregulatedspeedandpersistence.Blockingβ2integrinsofcellsmigratingonFnidentifiedanunderlyingβ2‐integrin‐directedmodulationofpersistence.Thesedatademonstratethatindividualcomponentsoftheneutrophilchemotacticresponseshowintegrindependenceandarefinelytunablewithdifferentligand,mechanotactic,andchemotacticcues,underscoringtheneedforsensitiveanalyticalmethods...

[学科分类] 生理学

[关键词] integrins;migration;mechanosensing;biophysics