Title: Dynein catch bond as a mediator of codependent bidirectional cellular transport,
Abstract: Intracellular bidirectional transport of cargo on Microtubule filaments is
achieved by the collective action of oppositely directed dynein and kinesin
motors. Experimental investigations probing the nature of bidirectional
transport have found that in certain cases, inhibiting the activity of one type
of motor results in an overall decline in the motility of the cellular cargo in
both directions. This somewhat counter-intuitive observation, referred to as
paradox of codependence is inconsistent with the existing paradigm of a
mechanistic tug-of-war between oppositely directed motors. Existing theoretical
models do not take into account a key difference in the functionality of
kinesin and dynein. Unlike kinesin, dynein motors exhibit catchbonding, wherein
the unbinding rates of these motors from the filaments are seen to decrease
with increasing force on them. Incorporating this catchbonding behavior of
dynein in a theoretical model and using experimentally relevant measures
characterizing cargo transport, we show that the functional divergence of the
two motors species manifests itself as an internal regulatory mechanism for
bidirectional transport and resolves the paradox of codependence. Our model
reproduces the key experimental features in appropriate parameter regimes and
provides an unifying framework for bidirectional cargo transport.