Cellular Cytoskeletal Motor Proteins 1211 Co-operative transport by molecular motors Florian Berger* 1 , Corina Keller*, Melanie J.I. M ¨ uller†, Stefan Klumpp* and Reinhard Lipowsky* *Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany, and †Physics Department, Harvard University, Cambridge, MA 02138, U.S.A. Abstract Intracellular transport is often driven co-operatively by several molecular motors, which may belong to one or several motor species. Understanding how these motors interact and what co-ordinates and regulates their movements is a central problem in studies of intracellular transport. A general theoretical framework for the analysis of such transport processes is described, which enables us to explain the behaviour of intracellular cargos by the transport properties of individual motors and their interactions. We review recent advances in the theoretical description of motor co-operativity and discuss related experimental results. Introduction The complex internal structure of cells depends, to a large extent, on active transport by molecular motors. In many cases, the transport of cellular cargos such as RNAs, protein complexes, filaments and organelles relies on the co-operative action of several molecular motors [1]. Furthermore, many cargos exhibit bidirectional movements that involve two motor species that move in opposite directions, for example, kinesin-1 and cytoplasmic dynein, or switch between microtubule-based and actin-based transport. How multiple motors are co-ordinated, in particular when the transport involves two or more species of motors, is currently an area of active research. In the present review, we discuss three different scenarios for co-operative transport from a theoretical perspective. The three cases are as follows: unidirectional transport by one team of motors, bidirectional transport by two teams of motors and transport on different tracks, involving both actin- and microtubule-based motors. All three cases have been studied extensively in recent years, both experimentally [2–7] and theoretically [8–10]. Theoretical approaches can contribute to the study of motor co-operation in several ways. One important objective of theory is to integrate the well-established properties of individual motors into comprehensive models for co-operative transport. The comparison of quantitative theoretical predictions and experiments can then provide insights into mechanistic details that are not directly accessible experimentally. For example, experiments usually trace the trajectory of a cargo, which may have a complex relationship with the movements of the individual motors, since several different motor configurations may lead to the same cargo behaviour. In this case, theoretical models can provide a link between the behaviour on the cargo level and the behaviour of the individual motors working collectively. In general, theory also provides a conceptual framework for the analysis of experimental results; even if it is not predictive in a quantitative manner, it can still suggest how to analyse Key words: bidirectional transport, co-operative transport, diffusive linker, molecular motor, stochastic modelling, tug-of-war. 1 To whom correspondence should be addressed (email florian.berger@mpikg.mpg.de). data. In the following, examples of the interplay between theory and experiment are provided, which we expect to be useful for gaining an improved understanding of co-operative intracellular transport. Unidirectional transport Even though a single motor molecule can power processive motion, transport in cells is often driven by more than one motor [1]. One advantage of cargo transport by several motors is a higher velocity if the cargo experiences a high viscosity [8,12]. Another advantage of co-operative transport is an increased run length compared with the run length of a single motor, which is typically 1 μm: if one motor unbinds, the cargo is still transported by the other motors and the unbound motor has a chance to rebind to the filament. In this way, cargos can be transported over typical cellular distances of tens of micrometres. Using a simple but rather general model that relates the parameters of cargo transport to the properties of the individual motors, we have derived a relationship between the run length and the number of motors pulling the cargo that indicates that the run length increases exponentially with the number of motors [8]. Qualitatively, an increase in the run length has been known for a long time [13,14], but quantitative experiments remain challenging, because it is difficult to determine the number of motors involved in the transport. Two previous studies of the run lengths of beads covered with different amounts of kinesin-1 have attempted to estimate the motor number on the basis of force measurements [15] or run length distributions [2]. While the observations from the latter study were consistent with the theoretical predictions, the former study found longer run lengths than expected. However, in both studies only the average number of motors could be determined and the actual number of engaged motors varied from bead to bead. Furthermore, the precise geometric arrangement of the motors was not known. These difficulties have been overcome in a recent study that used synthetic complexes of two kinesin motors connected through a rigid DNA scaffold [3]. The dynamics Biochem. Soc. Trans. (2011) 39, 1211–1215; doi:10.1042/BST0391211 C  The Authors Journal compilation C  2011 Biochemical Society