Our study of the effects of the cargo on transport has a number of ‘take-home’ messages. The first is that, at both the single-motor and multiple-motor levels, the presence of the cargo can significantly alter the effective ‘on’ rate/probability of successful binding of the motor(s) to the filament, because the center of mass of the cargo diffuses away from the microtubule relatively slowly, and while this is occurring, its rotational diffusion frequently brings the motor close enough to the microtubule to allow attachment. Thus, the cargo ‘helps’ the motor to attach, though the degree of assistance depends on cargo size and viscosity of the medium surrounding the cargo. Rapidly diffusing cargos might not linger long in the vicinity of a microtubule, but in a cell where there are multiple filaments available, these cargos could quickly find and bind to a filament.
Second, in order to for a motor to attach to the filament in a reasonable amount of time, the motor length needs to be longer or comparable to the radius of the cargo which may explain why motors are 60 to 110 nm in length.
Third, if motors are randomly arranged on the cargo's surface, the relationship between the number of motors present and the number of actually engaged motors depends strongly on the cargo size, so that different simple models of regulating cargo motion by recruiting motors to the cargo surface (either by a specified change in total number of motors, or by a specified change in local motor surface density) will have different effects on overall cargo motion as a function of cargo size. Thus, in order to have regulation affect a set of cargos equally, independent in variations in cargo size, it is best to have motors clustered in a small region on the cargo.
A further finding also supports the utility of motor clustering: for large cargos, if motors are randomly placed, achieving a reasonable number of engaged motors (n
3–6) would require a large number of motors (50–100) to be present on the cargo, which appears inconsistent with biochemical characterizations of cargo-bound microtubule motors 
, though it is consistent with biochemical characterizations of cargo-bound myosin motors 
which are likely randomly arranged on cargos 
. Overall, our findings suggest that, in vivo
, microtubule motors are likely organized into clusters when present on large cargos, but that such clustering is unnecessary for small cargos.
In addition, a reasonable number of engaged motors would be required for long travel distances of several microns but not for short run lengths. Since microtubules can be tens of microns long compared to actin filaments which have a typical decay length of 1.6 microns 
, we expect long travel distances along microtubules but relatively short run lengths along actin filaments. Thus we predict the microtubule motors kinesin and dynein to be clustered on cargos while we expect the actin motor myosin V to bind randomly to cargos. There is clear experimental evidence for the random arrangement of myosin on cargos in vivo
, and weak experimental evidence for the clustering of kinesin and cytoplasmic dynein 
For the purposes of this paper, we have assumed that the points where motors are attached to the cargos are fixed on the cargo's surface. This is true in some cases, e.g., when motors bind to dynactin which in turn binds to spectrin which is a filament that coats some vesicles 
. However, in other cases, the attachment points can diffuse through the fluid membrane of the vesicle and cluster at one location. An example of this is an experiment showing that motors dynamically accumulate at the tip of membrane tubes growing out of a vesicle as a consequence of the fluidity of the membrane 
Clustering does not seem to affect the rate at which the first motor of a cargo attaches to a microtubule unless the cargo is large (greater than 200 nm) and the viscosity is high. Motor proteins are sufficiently long (greater than 50 nm) and rotational diffusion sufficiently rapid that the number of motors on a cargo does not significantly affect the rate at which the cargo binds to the microtubule.