  Intracellular transport is an essential function in eucaryotic cells,
facilitated by motor proteins - proteins converting chemical energy into
kinetic energy. It is known that motor proteins work in teams enabling
unidirectional and bidirectional transport of intracellular cargo over long
distances. Disruptions of the underlying transport mechanisms, often caused by
mutations that alter single motor characteristics, are known to cause
neurodegenerative diseases. For example, phosphorylation of kinesin motor
domain at the serine residue is implicated in Huntington's disease, with a
recent study of phosphorylated and phosphomimetic serine residues indicating
lowered single motor stalling forces. In this article we report the effects of
mutations of this nature on transport properties of cargo carried by multiple
wild-type and mutant motors. Results indicate that mutants with altered stall
forces might determine the average velocity and run-length even when they are
outnumbered by wild type motors in the ensemble. It is shown that mutants gain
a competitive advantage and lead to an increase in expected run-length when
load on the cargo is in the vicinity of the mutant's stalling force or a
multiple of its stalling force. A separate contribution of this article is the
development of a semi-analytic method to analyze transport of cargo by multiple
motors of multiple types. The technique determines transition rates between
various relative configurations of motors carrying the cargo using the
transition rates between various absolute configurations. This enables exact
computation of average velocity and run-length. It can also be used to
introduce alterations of various single motor parameters to model a mutation
and to deduce effects of such alterations on the transport of a common cargo by
multiple motors. Our method is easily implementable and we provide a software
package for general use.
