title: Stepping, strain gating, and an unexpected force-velocity curve for multiple-motor-based transport.
abstract: BACKGROUND
  Intracellular transport via processive kinesin, dynein, and myosin molecular motors plays an important role in maintaining cell structure and function. In many cases, cargoes move distances longer than expected for single motors; there is significant evidence that this increased travel is in part due to multiple motors working together to move the cargoes. Although we understand single motors experimentally and theoretically, our understanding of multiple motors working together is less developed.
  
  
  RESULTS
  We theoretically investigate how multiple kinesin motors function. Our model includes stochastic fluctuations of each motor as it proceeds through its enzymatic cycle. Motors dynamically influence each other and function in the presence of thermal noise and viscosity. We test the theory via comparison with the experimentally observed distribution of step sizes for two motors moving a cargo, and by predicting slightly subadditive stalling force for two motors relative to one. In the presence of load, our predictions for travel distances and mean velocities are different from the steady-state model: with high motor-motor coupling, we predict a form of strain-gating, where-because of the underlying motor's dynamics-the motors share load unevenly, leading to increased mean travel distance of the multiple-motor system under load. Surprisingly, we predict that in the presence of small load, two-motor cargoes move slightly slower than do single-motor cargoes. Unpublished data from G.T. Shubeita, B.C. Carter, and S.P.G. confirm this prediction in vivo.
  
  
  CONCLUSIONS
  When only a few motors are active, fluctuations and unequal load sharing between motors can result in significant alterations of ensemble function.
authors.affiliation: Department of Developmental and Cell Biology, University of California, Irvine, California 92697, USA.
authors.forename: Ambarish
authors.initials: A
authors.lastname: Kunwar
authors.forename: Michael
authors.initials: M
authors.lastname: Vershinin
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.forename: Steven P
authors.initials: SP
authors.lastname: Gross
mesh_terms: D001692:Biological Transport; D001696:Biomechanical Phenomena; D003198:Computer Simulation; D016547:Kinesins / Q000378:metabolism*; D008958:Models, Molecular; D014783:Viscosity
chemical_list: D016547:Kinesins