Modelling effects of internalized antibody: a simple comparative study

Abstract

BackgroundThe modelling framework is proposed to study protection properties of antibodies to neutralize the effects of the plant toxin (ricin). The present study extends our previous work by including (i) the model of intracellular transport of toxin to the Endoplasmic Reticulum and (ii) the model of the internalised antibodies (when antibody is delivered directly into the cytosol).MethodSimulation of the receptor-toxin-antibody interaction is implemented by solving the systems of PDEs (advection-diffusion models) or ODEs (rate models) for the underlying transport coupled with mass-action kinetics.ResultsAs the main application of the enhanced framework we present a comparative study of two kinds (external and internalised) of antibodies. This comparison is based on calculation of the non-dimensional protection factor using the same set of parameters (geometry, binding constants, initial concentrations of species, and total initial amount of the antibody).ConclusionThis research will provide a framework for consistent evaluation and comparison of different types of antibodies for toxicological applications.

Modeling of toxin–antibody interaction and toxin transport toward the endoplasmic reticulum

“…In the present paper, assuming that toxin and antibody are initially delivered in the extracellular domain, we refine our previous model [7] additionally involving the pinocytotic toxin internalization from the extracellular to the intracellular space (cellular drinking), toxin clearance (removal from the system) flux, the lysosomal toxin degradation, and the intact toxin exocytotic recycling back to the extracellular space. Contrary to the model proposed in [7] exploiting the advective-diffusive toxin transport in the intracellular domain i , we follow the paper [16] (or the more general one [17]) devoted to the intracellular transport of vesicles and organelles and assume that all toxin particles are divided into two populations: those that are attached to the microtubules of the cell skeleton and those that are detached from them.…”

“…Contrary to the model proposed in [7] exploiting the advective-diffusive toxin transport in the intracellular domain i , we follow the paper [16] (or the more general one [17]) devoted to the intracellular transport of vesicles and organelles and assume that all toxin particles are divided into two populations: those that are attached to the microtubules of the cell skeleton and those that are detached from them. The detached particles are assumed to undergo diffusion.…”

“…The advective step of toxin transport used in [7] simulates the toxin retrograde (dynein-driven) movement toward the ER.…”

“…The development and production of new antibodies is an expensive process that usually includes extensive experimental studies. In order to reduce this experimental burden, a simple modeling framework has recently been proposed [6][7][8][9] that enables extensive studies to increase the protective potential of antibodies before proceeding with targeted experimental studies.…”

“…The modeling framework proposed in [6,7] involves toxin, antibody, and their nontoxic complex diffusive transport in the extracellular domain, receptor-mediated toxin internalization, and intracellular toxin motion based on the diffusion-advection mechanisms towards the ER. The advective step of toxin transport used in [7] simulates the toxin retrograde (dynein-driven) movement toward the ER.…”