title: Natural promoters of calcium oxalate monohydrate crystallization.
abstract: Crystallization is often facilitated by modifiers that interact with specific crystal surfaces and mediate the anisotropic rate of growth. Natural and synthetic modifiers tend to function as growth inhibitors that hinder solute attachment and impede the advancement of layers on crystal surfaces. There are fewer examples of modifiers that operate as growth promoters, whereby modifier-crystal interactions accelerate the kinetic rate of crystallization. Here, we examine two proteins, lysozyme and lactoferrin, which are observed in the organic matrix of three types of pathological stones: renal, prostatic, and pancreatic stones. This work focuses on the role of these proteins in the crystallization of calcium oxalate monohydrate (COM), the most prominent constituent of human kidney stones. Using a combination of experimental techniques, we show that these proteins, which are rich in l-arginine and l-lysine amino acids, promote COM growth. The synthesis and testing of peptides derived from contiguous segments of lysozyme's primary amino acid sequence revealed subdomains within the protein that operate either as an inhibitor or promoter of COM growth, with the latter exhibiting efficacies that nearly match that of the protein. We observed that cationic proteins promote COM growth over a wide range of modifier concentration, which differs from calcification promoters in the literature that exhibit dual roles as promoters and inhibitors at low and high concentration, respectively. This seems to suggest a unique mechanism of action for lysozyme and lactoferrin. Possible explanations for their effects on COM growth and crystal habit are proposed on the basis of classical colloidal theories and the physicochemical properties of peptide subdomains, including the number and spatial location of charged or hydrogen-bonding moieties.
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Houston , Houston, Texas 77204, United States.
authors.forename: Sahar
authors.initials: S
authors.lastname: Farmanesh
authors.forename: Jihae
authors.initials: J
authors.lastname: Chung
authors.forename: Ricardo D
authors.initials: RD
authors.lastname: Sosa
authors.forename: Jun Ha
authors.initials: JH
authors.lastname: Kwak
authors.forename: Pankaj
authors.initials: P
authors.lastname: Karande
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Rimer