Behaviour of the model antibody fluid constrained by rigid spherical obstacles. Effects of the obstacle--antibody attraction

TL;DR

This paper investigates how rigid spherical obstacles with attractive interactions influence the phase behavior and percolation of monoclonal antibody fluids, revealing complex effects of obstacle-antibody attraction on critical properties.

Contribution

It introduces a combined theoretical approach to analyze the impact of attractive obstacle interactions on antibody fluid phase separation and percolation thresholds.

Findings

Obstacles decrease critical density and temperature of the antibody fluid.

Attractive obstacle interactions initially widen and then narrow the temperature-density envelope.

Critical point behavior is non-monotonic with increasing obstacle-antibody attraction.

Abstract

This study is concerned with behaviour of fluid of monoclonal antibodies (mAbs) when trapped in a confinement represented by rigid spherical obstacles that attract proteins. The antibody molecule is depicted as an assembly of seven hard spheres, organized to resemble Y shaped molecule. The antibody has two Fab and one Fc domains located in the corners of letter Y. In this calculation, only the Fab-Fab and Fab-Fc attractive pair interactions are effective. The confinement is formed by the randomly distributed hard-spheres fixed in space. The spherical obstacles, besides the size exclusion, also interact by the Yukawa attractive interaction with with each bead of the antibody molecule. We applied the combination of the scaled-particle theory, Wertheim's thermodynamic perturbation theory and the Flory-Stockmayer theory to calculate: (i) the liquid-liquid phase separation, and (ii) the percolation threshold. All these quantities were calculated as functions of the strength of the attraction between the monoclonal antibodies, and monoclonal antibodies and obstacles. The conclusion is that while the hard-sphere obstacles decrease the critical density as also, the critical temperature of the mAbs fluid, the effect of the protein-obstacle attraction is more complex. Adding the attraction to obstacle-mAbs interaction first increases the wideness of the temperature-density envelope. However, with the further increase of the obstacle-mAbs attraction intensity we observe reversal of the effect, the temperature-density curves become narrower. At some point, depending on the AC=BC interaction, the situation is observed where two different temperatures have the same fluid density (reentry point ). In all the cases shown here the critical point decreases below the value for the neat fluid, but the behaviour with respect to increase of the strength of obstacle-mAbs attraction is not monotonic.