Transport Properties of Melanosomes along Microtubules Interpreted by a Tug-of-War Model with Loose Mechanical Coupling

SEBASTIÁN BOUZAT; VALERIA LEVI; LUCIANA BRUNO

PLOS ONE

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2012 vol. 7 p. 1 - 16

1932-6203

In this work, we explored theoretically the transport of organelles driven along microtubules by molecular motors ofopposed polarities using a stochastic model that considers a Langevin dynamics for the cargo, independent cargo-motorlinkers and stepping motion for the motors. It has been recently proposed that the stiffness of the motor plays an importantrole when multiple motors collectively transport a cargo. Therefore, we considered in our model the recently reportedvalues for the stiffness of the cargo-motor linker determined in living cells (,0.01 pN/nm, [1]) which is significantly lowerthan the motor stiffness obtained in in vitro assays and used in previous studies. Our model could reproduce the multimodalvelocity distributions and typical trajectory characteristics including the properties of the reversions in the overall directionof motion observed during melanosome transport along microtubules in Xenopus laevis melanophores. Moreover, weexplored the contribution of the different motility states of the cargo-motor system to the different modes of the velocitydistributions and could identify the microscopic mechanisms of transport leading to trajectories compatible with thoseobserved in living cells. Finally, by changing the attachment and detachment rates, the model could reproduce the differentvelocity distributions observed during melanosome transport along microtubules in Xenopus laevis melanophoresstimulated for aggregation and dispersion. Our analysis suggests that active tug-of-war processes with loose mechanicalcoupling can account for several aspects of cargo transport along microtubules in living cells.