A Deterministic Mathematical Model for Bidirectional Excluded Flow with Langmuir Kinetics

TL;DR

This paper introduces a new deterministic model for bidirectional cellular transport with Langmuir kinetics, showing it has a unique stable equilibrium and analyzing effects like ribosome drop-off on flow and protein production.

Contribution

The paper develops a novel deterministic mean-field model for bidirectional exclusion processes with Langmuir kinetics, including stability and entrainment analysis.

Findings

Model admits a unique globally stable equilibrium.

System entrains to periodic rate variations.

Ribosome drop-off reduces protein production rate.

Abstract

In many important cellular processes, including mRNA translation, gene transcription, phosphotransfer, and intracellular transport, biological "particles" move along some kind of "tracks". The motion of these particles can be modeled as a one-dimensional movement along an ordered sequence of sites. The biological particles (e.g., ribosomes, RNAPs, phosphate groups, motor proteins) have volume and cannot surpass one another. In some cases, there is a preferred direction of movement along the track, but in general the movement may be two-directional, and furthermore the particles may attach or detach from various regions along the tracks (e.g. ribosomes may drop off the mRNA molecule before reaching a stop codon). We derive a new deterministic mathematical model for such transport phenomena that may be interpreted as the dynamic mean-field approximation of an important model from mechanical statistics called the asymmetric simple exclusion process (ASEP) with Langmuir kinetics. Using tools from the theory of monotone dynamical systems and contraction theory we show that the model admits a unique globally asymptotically stable equilibrium. This means that the occupancy in all the sites along the lattice converges to a steady-state value that depends on the parameters but not on the initial conditions. We also show that the model entrains (or phase locks) to periodic excitations in any of its forward, backward, attachment, or detachment rates. We demonstrate an application of this phenomenological transport model for analyzing the effect of ribosome drop off in mRNA translation. One may perhaps expect that drop off from a jammed site may increase the total flow by reducing congestion. Our results show that this is not true. Drop off has a substantial effect on the flow, yet always leads to a reduction in the steady-state protein production rate.