Dynamic kinesin-1 clustering on microtubules due to mutually attractive interactions

Abstract

Molecular motors often work collectively inside the cell. While the properties of individual motors have been extensively studied over the last decade, much less is known on how motors coordinate their action when working in ensembles. The motor collective behaviour in conditions where they contact each other, as in intracellular transport, may strongly depend on their mutual interactions. In particular, mutual interactions may result in motor clustering without the need of additional proteins. Here we study the interactions between kinesin-1 molecules by analysing their attachment/detachment kinetics on microtubules in the absence of motor motion. Our in vitro experiments show that kinesins-1 remain longer attached to the microtubule in the presence of neighbouring motors, resulting in the formation of motor clusters. Numerical simulations of the motor attachment/detachment dynamics show that the presence of attractive interactions between motors quantitatively accounts for the experimental observations. From the comparison of the numerical results and the experimental data we estimate the interaction energy between kinesin-1 molecules to be 1.6 +/- 0.5K(B)T. The existence of attractive interactions between kinesins-1 provides a new insight into the coordination mechanism between motor proteins and may be crucial to understand the large scale traffic in cells.

Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

“…There is no direct measurement of this interaction strength yet. Very crude estimates made from the experiments in [268] and [311] would give too low values. However, more experimental data would be necessary before giving a conclusive statement.…”

“…Indeed, for conventional kinesin, there is evidence for a mutual attractive interaction between motor proteins, so that a kinesin preferentially binds to the MT in the vicinity of other kinesins [375,268,311]. The strength of the interaction between two kinesin-1 molecules has been estimated at 1.6 ± 0.5 k B T [311].…”

A parity breaking Ising chain Hamiltonian as a Brownian motor

“…Beyond the hard-core repulsion, this interaction is, at least for U 2 , U 3 > 0, essentially attractive: in order to minimize the energy, particles prefer to cluster together. The precise form of these interactions was of course motivated only by the simplicity of expression (1) rather than by biophysical considerations; nevertheless, experiments [33] seem to suggest that motor proteins interact locally via short-range potentials that are weakly attractive and lead to 'motor clustering'.…”

Elucidating the molecular mechanisms underlying cellular response to biophysical cues using synthetic biology approaches

“…80 Other examples include an assembled 2D network of microtubules on pillars, which was utilized in a combined fluorescence study to investigate the interaction between the kinesin motors themselves. 81 Using micropillars and super-resolution fluorescence microscopy it was discovered that there exists attractive interactions between kinesin motors, resulting in motor clustering along the microtubule as shown in Figure 5. Understanding motor protein interactions is critical when considering intracellular transport mechanisms, and controlled in vitro conditions now allow for directly probing collective motor behavior.…”