Environmental control of microtubule-based bidirectional cargo-transport

Inside cells, various cargos are transported by teams of molecular motors. Intriguingly, the motors involved generally have opposite pulling directions, and the resulting cargo dynamics is a biased stochastic motion. It is an open question how the cell can control this bias. Here we develop a model which takes explicitly into account the elastic coupling of the cargo with each motor. We show that bias can be simply controlled or even reversed in a counterintuitive manner via a change in the external force exerted on the cargo or a variation of the environmental properties. Furthermore, the superdiffusive behavior found at short time scales indicates the emergence of motor cooperation induced by cargo-mediated coupling. Introduction. – In cells, most of the active transport processes, which are essential for cellular functions, are driven by molecular motors. These molecular motors are proteins having the ability to move preferentially in a defined direction on the polar filaments of the cytoskeleton [1]. The three most well-known molecular motors’ families involved in transport are myosins, which move on actin filaments, dyneins and kinesins, which use microtubules (MT) as tracks [2]. Kinesin motors are stepping preferentially toward the growing (or plus-) end of MTs while dynein motors walk in the opposite direction. Molecular motors can step individually or transport cargos along the cytoskeletal filaments. In order to generate forces large enough [3] to move a big cargo in the crowded environment of the cell, cargos are often transported by teams of molecular motors [4]. This is obviously beneficial if motors of the same type are attached to the cargo, since the force can be distributed between them. It enhances the processivity of the cargo and its ability to resist against forces emerging when transporting the cargo. In many cases, however, motors that are attached to a given cargo pull in opposite preferential directions. Surprisingly, the attachment of two kinds of motors is not only observed for objects like mitochondria, which have to be spread out in the whole cell volume [5], but also for cargos which have a definite target, for example to be transported from the cell center to the membrane or vice versa [6]. Although the attachment of two kinds of motors should enable bidirectional transport it is expected that, due to the difference in the characteristics of the various types of motors attached to the cargo [7] and possibly in the number of attached motors, the cargo undergoes a biased stochastic walk if the MT network is oriented. Depending on the given motor-cargo system and the environment of the filaments different types of motion have been observed, which can be controlled by different mechanisms. Some pigment cells (melanosomes) for example have the ability to switch between two states, in which the pigments are either dispersed or aggregated at one extremity of the filaments [8, 9]. The mechanisms that allow for such a transition from a non-biased to a biased motion are not yet well understood but have been related to signaling processes which regulate the activity of the attached motors [10]. Next to the active regulation of the motor dynamics, for example in cell signaling processes, also the cellular environment plays an important role. Recent in vivo experimental studies on cargos transported bidirectionally have revealed a very complex dynamical behavior. Superas well as subdiffusive regimes of the cargos’ trajectories