Abstract Hematin crystallization is an essential element of heme detoxification of malaria parasites and its inhibition by antimalarial drugs is a common treatment avenue. We demonstrate at biomimetic conditions in vitro irreversible inhibition of hematin crystal growth due to distinct cooperative mechanisms that activate at high crystallization driving forces. The evolution of crystal shape after limited-time exposure to both artemisinin metabolites and quinoline-class antimalarials indicates that crystal growth remains suppressed after the artemisinin metabolites and the drugs are purged from the solution. Treating malaria parasites with the same agents reveals that three- and six-hour inhibitor pulses inhibit parasite growth with efficacy comparable to that of inhibitor exposure during the entire parasite lifetime. Time-resolved in situ atomic force microscopy (AFM), complemented by light scattering, reveals two molecular-level mechanisms of inhibitor action that prevent β-hematin growth recovery. Hematin adducts of artemisinins incite copious nucleation of nonextendable nanocrystals, which incorporate into larger growing crystals, whereas pyronaridine, a quinoline-class drug, promotes step bunches, which evolve to engender abundant dislocations. Both incorporated crystals and dislocations are known to induce lattice strain, which persists and permanently impedes crystal growth. Nucleation, step bunching, and other cooperative behaviors can be amplified or curtailed as means to control crystal sizes, size distributions, aspect ratios, and other properties essential for numerous fields that rely on crystalline materials.
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Crystal Shape Control on the Repacking and Jamming of Crystal‐Rich Mushes
Abstract The rheology of crustal mushes is a crucial parameter controlling melt segregation and magma flow. However, the relations between mush dynamics and crystal size and shape distribution remain poorly understood because of the complexity of melt‐crystal and crystal‐crystal interactions. We performed analog experiments to characterize the mechanisms that control pore space reduction associated with repacking. Three suspensions of monodisperse particles with different geometries and aspect ratios (1:1, 2:1, 4:1) in a viscous fluid were tested. Our results show that particle aspect ratios strongly control the melt extraction processes. We identify two competing mechanisms that enable melt extraction at grain scale. The first mechanism leads to continuous deformation and melt extraction and is associated with “diffuse” frictional dissipation between neighboring particles. The second is stochastic, localized, and nearly instantaneous and is associated with the development and destruction of force chains percolating through the granular assembly.
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- PAR ID:
- 10444132
- Publisher / Repository:
- DOI PREFIX: 10.1029
- Date Published:
- Journal Name:
- Geophysical Research Letters
- Volume:
- 49
- Issue:
- 19
- ISSN:
- 0094-8276
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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