1. Mechanisms underlying cargo transport through MT-MT intersections
The microtubule network inmanycells takesthe formof a3D mesh and iscomprisedof an
interconnectedsetof MT-MT crossingsfeaturinghighlyvariable anglesandseparationdistances. At
each crossing,arobustlymovingcargoencountersa metaphorical forkinthe road: passor switch? The
cargo’s navigational outcomeisknowntobe highlysensitivetothe intersection’s3Dgeometry;even
seeminglytrivialnetwork changescanperturb overall cargoroutingwhichcouldpotentially addupto
playa significantrole in variouspathologies. Forexample, the densityof the MT network significantly
affectsinsulinsecretioninpancreaticβ-cells. Therefore,ourvisionis todescribe local mechanisms
underlyingcargonavigationthroughasingle crossingandthentoextendourfindingsto a global cargo
routingmodel.Toadvance thisvision,we usedin vitro holographicoptical trappingto constructvarious
3D MT-MT crossings coveringacomprehensive range of anglesandseparationdistances. We then
measuredthe statisticsof cargonavigation outcomes acrosseachintersection geometry. Ourcontrolled
experimentsallowedusto performhighlyconstrainedsimulationswhichhelp provide amechanistic
understandingof cargonavigation. We will presentourexperimental andtheoretical resultsand discuss
howour findingscanbe scaled upto cellular-level transport.