Multiple Interacting Kinesin-1 Motors Cooperate Negatively

Abstract

Many sub-cellular commodities are transported by more than one motor, and it is well-known that the combined function of motors can lead to unique transport behaviors. Yet, little is known about how grouping multiple motor proteins influences the motile properties of cargos, and in particular, relationships between the structural / compositional organization of motor complexes and key collective transport parameters (run lengths, detachment forces) have not been established.We have taken important steps towards solving this problem by synthesizing the first set of structurally-defined complexes of interacting kinesin-1 motors. Furthermore, we have developed ‘single-molecule’ assays that can examine new and important aspects of collective motor dynamics; namely, whether multiple motors cooperate in a positive or negative fashion and if these behaviors influence ensemble transport properties of multiple motor systems. Herein, we demonstrate that interactions among two elastically-coupled kinesin molecules lead to negative motor cooperativity, and that this behavior influences collective motor force production. We also describe how such effects can reconcile differences between measurements of cargo motions in vitro and in living cells.