Specificity of Growth Inhibitors and their Cooperative Effects in Calcium Oxalate Monohydrate Crystallization

The
molecular recognition and interactions governing site-specific
adsorption of growth inhibitors on crystal surfaces can be tailored
in order to control the anisotropic growth rates and physical properties
of crystalline materials. Here we examine this phenomenon in calcium
oxalate monohydrate (COM) crystallization, a model system of calcification
with specific relevance for pathological mineralization. We analyzed
the effect of three putative growth inhibitorschondroitin
sulfate, serum albumin, and transferrinusing analytical techniques
capable of resolving inhibitor–crystal interactions from interfacial
to bulk scales. We observed that each inhibitor alters surface growth
by adsorbing on to distinct steps emanating from screw dislocations
on COM surfaces. Binding of inhibitors to different crystallographic
faces produced morphological modifications that are consistent with
classical mechanisms of layer-by-layer crystal growth inhibition.
The site-specific adsorption of inhibitors on COM surfaces was confirmed
by bulk crystallization, fluorescent confocal microscopy, and atomic
force microscopy. Kinetic studies of COM growth at varying inhibitor
concentrations revealed marked differences in their efficacy and potency.
Systematic analysis of inhibitor combinations, quantified via the
combination index, identified various binary pairings capable of producing
synergistic, additive, and antagonistic effects. Collectively, our
investigation of physiologically relevant biomolecules suggests potential
roles of COM inhibitors in pathological crystallization and provides
guiding principles for biomimetic design of molecular modifiers for
applications in crystal engineering.