Vesicle aggregation by multivalent ligands: relating crosslinking ability to surface affinity

Abstract

In an effort to improve the stability of our tissue-mimetic vesicle aggregates, we have investigated how increasing the valency of our multivalent crosslinking ligand, poly-l-histidine, affected both the extent of vesicle aggregation and the affinity of the multivalent ligand for the synthetic receptor Cu(1) embedded in the vesicle membranes. Although increasing ligand valency gave the anticipated increase in the size of the vesicle aggregates, isothermal calorimetric studies did not show the expected increase in the valence-corrected binding constant for the embedded receptors. To explain both observations, we have developed a simple new binding model that encompasses both multivalent binding to receptors on a single vesicle surface (intramembrane binding) and vesicle crosslinking (intermembrane binding).