Competing discrete interfacial effects are critical for amyloidogenesis Export

@article{Jean_FASEBJ09, abstract = {Amyloid accumulation is associated with pathological conditions, including type II diabetes and Alzheimer's disease. Lipids influence amyloidogenesis and are themselves targets for amyloid-mediated cell membrane disruption. Amyloid precursors are surface-active, accumulating at hydrophobic-hydrophilic interfaces (e.g., air-water), where their biophysical and kinetic behaviors differ from those in the bulk solution with significant and underappreciated consequences. Biophysical modeling predicted the probability and rate of {beta}-sheet amyloid dimer formation to be higher and faster at the air-water interface (AWI) than in the bulk (by 14 and [\~{}]1500 times, respectively). Time-course staining experiments with a typical amyloid dye verified our predictions by demonstrating that without AWI, islet amyloid polypeptide (IAPP) fibrilization was abolished or slowed, depending on the conditions. Our controls included undisturbed IAPP reactions, and we ascertained that the AWI removal process (technical or material) did not itself affect the reaction. Furthermore, we showed that the role of membranes in amyloidogenesis has been previously underestimated; in an in vivo-like situation (with no AWI), anionic liposomes (containing dioleoylphosphatidylglycerol) enhanced IAPP fibrilogenesis far more than described previously in conventional assay conditions (in the presence of an AWI). These findings have implications for the protein misfolding field and in assay design to target toxic protein aggregation.--Jean, L., Lee, C. F., Lee, C., Shaw, M., Vaux, D. J. Competing discrete interfacial effects are critical for amyloidogenesis. 10.1096/fj.09-137653}, author = {Jean, Letitia and Lee, Chiu F. and Lee, Chongsoo and Shaw, Michael and Vaux, David J.}, citeulike-article-id = {5866476}, citeulike-linkout-0 = {http://dx.doi.org/10.1096/fj.09-137653}, citeulike-linkout-1 = {http://www.fasebj.org/content/fj.09-137653v1/.abstract}, citeulike-linkout-2 = {http://www.fasebj.org/content/fj.09-137653v1/.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/19741169}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=19741169}, day = {9}, doi = {10.1096/fj.09-137653}, journal = {FASEB J.}, keywords = {amyloid, dynamics, experimental, interfacial\_effects, kinetics, nucleation, theory}, month = {September}, pages = {fj.09-137653+}, posted-at = {2009-10-01 11:08:09}, priority = {2}, title = {Competing discrete interfacial effects are critical for amyloidogenesis}, url = {http://dx.doi.org/10.1096/fj.09-137653}, year = {2009} }

TY - JOUR ID - Jean_FASEBJ09 L3 - citeulike-article-id:5866476 N2 - Amyloid accumulation is associated with pathological conditions, including type II diabetes and Alzheimer's disease. Lipids influence amyloidogenesis and are themselves targets for amyloid-mediated cell membrane disruption. Amyloid precursors are surface-active, accumulating at hydrophobic-hydrophilic interfaces (e.g., air-water), where their biophysical and kinetic behaviors differ from those in the bulk solution with significant and underappreciated consequences. Biophysical modeling predicted the probability and rate of {beta}-sheet amyloid dimer formation to be higher and faster at the air-water interface (AWI) than in the bulk (by 14 and [~]1500 times, respectively). Time-course staining experiments with a typical amyloid dye verified our predictions by demonstrating that without AWI, islet amyloid polypeptide (IAPP) fibrilization was abolished or slowed, depending on the conditions. Our controls included undisturbed IAPP reactions, and we ascertained that the AWI removal process (technical or material) did not itself affect the reaction. Furthermore, we showed that the role of membranes in amyloidogenesis has been previously underestimated; in an in vivo-like situation (with no AWI), anionic liposomes (containing dioleoylphosphatidylglycerol) enhanced IAPP fibrilogenesis far more than described previously in conventional assay conditions (in the presence of an AWI). These findings have implications for the protein misfolding field and in assay design to target toxic protein aggregation.--Jean, L., Lee, C. F., Lee, C., Shaw, M., Vaux, D. J. Competing discrete interfacial effects are critical for amyloidogenesis. 10.1096/fj.09-137653 JF - FASEB J. TI - Competing discrete interfacial effects are critical for amyloidogenesis SP - fj.09-137653 KW - amyloid KW - dynamics KW - experimental KW - interfacial_effects KW - kinetics KW - nucleation KW - theory AU - Jean, Letitia AU - Lee, Chiu AU - Lee, Chongsoo AU - Shaw, Michael AU - Vaux, David PY - 2009/09/09/ UR - http://dx.doi.org/10.1096/fj.09-137653 ER -