Developing new scientific initiatives centered on the design and fabrication of nanocrystalline materials, in areas ranging from photovoltaic technologies to therapeutic drug delivery, relies upon expanding fundamental, molecular-level understandings governing their self-assembly, application, and/or physiological function. Design is often challenged by the necessity for predictable and tailored control of material properties through a priori knowledge of growth kinetics and thermodynamics, intra-and inter-particle interactions and interfacial phenomena that regulate particle size, morphology, and polymorphism. Along these lines, research in my doctoral (Department of Chemical Engineering, University of Delaware) and postdoctoral (Molecular Design Institute, New York University) studies merge along a centralized theme of mechanistic investigations of crystallization. Collective results from these studies will be presented in this poster, highlighting (I) my doctoral research on developing predictive models for microporous silica growth from precursor solutions of self-assembled silica nanoparticles, and (II) postdoctoral research on identifying interactions and pathways governing kidney stone formation.

I. Mechanistic Investigations of Microporous Silicate Nucleation and Growth (Ph.D. Research at the University of Delaware)

Research efforts were focused on developing a molecular-level understanding of microporous silicate (i.e., zeolite) crystallization through combined experiments and modeling, concentrating largely on silica nanoparticles (2-6 nm) that are precursors, and possible building units ¹ in the synthesis of the all-silica zeolite, silicalite-1. Comprehensive analyses of nanoparticle self-assembly, nucleation, and growth were performed to gain mechanistic insight into their potential role in silicalite-1 crystallization. Protocols were established to measure silica phase behavior ², identifying the underlying physics governing nanoparticle formation, while simultaneously using a modeling strategy ³ that incorporates chemical equilibria and electrostatic interactions to quantify silica speciation, predict nanoparticle self-assembly, and provide a viable explanation for their colloidal stability. Small-angle scattering and calorimetry experiments were coupled to (i) examine the influence of structure-directing agents on nanoparticle self-assembly ⁴, (ii) measure kinetic rates and enthalpies of growth and dissolution, and (iii) probe compositional ⁵ and structural ⁶ changes that occur during the initial stages of nucleation.

A predictive silicalite-1 growth model was derived from experimental rate constants and kinetic rate expressions that incorporate chemical speciation, linking the mechanism to solution-mediated processes and quantitatively capturing growth rates over a wide range of reaction conditions. This poster will address these findings within the context of mechanisms proposed in the literature, highlighting advancements made toward characterizing processes integral to silicalite-1 formation. These research efforts also provided a methodology that we applied to studies of mesoporous silicate ⁷ and germanium-oxide nanoparticle 8 syntheses, ultimately serving as a framework toward rational syntheses of tailored nanomaterials and a template for expanding these techniques to areas such as biomimetics and biomineralization to better understand nature's ability to generate a host of exquisitely-structured materials.

II. Pathological Biomineralization of Kidney Stones (Postdoctoral Research at New York University)

Research in my postdoctoral work explores molecular-scale interactions at the surface of calcium oxalate monohydrate (COM) and cystine crystals (two common constituents of kidney stones) using atomic force microscopy (AFM) in an effort to ascertain their underlying mechanisms of formation. Kidney stones are polycrystalline aggregates that assemble through a series of events that include: nucleation, growth, aggregation, and crystal and/or aggregate attachment to epithelial cells. Integral and peripheral membrane proteins can mediate crystal-crystal contact, while a multitude of urinary proteins, polysaccharides, lipids, and cellular debris adsorb to crystal surfaces, likely acting as adhesive glue among aggregates.

Investigations of kidney stone pathogenesis involved (i) in vitro analyses of crystal growth to examine face-specific inhibitory effects in the presence of protein and macromolecular additives ⁹, and (ii) adhesion force measurements using AFM probes modified with biologically relevant functional groups to study surface-adsorbate interactions involved in crystal adhesion and aggregation ¹⁰. The latter were performed with functional groups that mimic L-arginine and L-glutamic acid residues, and in the presence of additives deemed to influence crystal growth and aggregation, focusing on two predominant urinary proteins: Tamm-Horsfall protein (THp) and osteopontin (OPN). Systematic studies of THp were performed to identify the affect of sialylated and glycoslated side chains on adhesion and growth, while dynamic protein unfolding measurements were conducted on OPN – a protein known to exhibit uncharacteristically strong adhesion to stone surfaces. Using established protocols in the literature for binding proteins to AFM tips, we have expanded the use of single amino-acid functionalized tips to directly measure protein-crystal and protein-protein interactions on stone surfaces. These combined results reveal new insights on physiological processes that regulate kidney stone formation, serving as a basis for future development of targeted drugs capable of inhibiting single crystal nucleation, dramatically reducing crystal growth rates or retention times, and/or preventing interparticle aggregation; thereby offering a generalized approach applicable to a variety of stone-forming crystals as well as analogous physiological diseases, such as gallstones.

References:

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9. Rimer, J.D., Lee, M.H., Wesson, J.A., Ward, M.D., In Preparation 2008

10. Rimer, J.D., Viswanathan, P., Wesson, J.A., Ward, M.D., In Preparation 2008