Prof. Jeffrey D. Rimer: "New Paradigms for the Prevention of Pathological Crystallization"

An efficient method to inhibit pathological crystallization is the identification of modifiers, which are (macro)molecules that reduce the rate of crystal growth. Here, I will discuss progress in understanding nonclassical pathways of crystallization and the design of effective modifiers as treatments of three human diseases: kidney stones, malaria, and atherosclerosis. One of the primary tools used to explore crystal growth mechanisms and modifier-crystal interfacial interactions is in situ atomic force microscopy, which we have coupled with microfluidics to assess modifier efficacy. Results from collaborative studies with computational and medical experts have identified unique crystallization pathways, mechanisms of crystal growth inhibition, and promising new therapies, such as the discovery of hydroxycitrate as an inhibitor of calcium oxalate kidney stones. Our studies revealed that hydroxycitrate induces strain in crystals, leading to localized dissolution. A similar outcome was observed for urate stones where solute isomers function as native growth inhibitors that can induce dramatic changes in crystal morphology, and suppress crystal growth at specific conditions. I will discuss new insights into studies of kidney stone prevention and highlight their similarities and differences with novel approaches we have been developing for controlled crystallization in malaria (i.e. heme crystals) and atherosclerosis (i.e. cholesterol crystals).