Kinetics of Different Processes in Human Insulin Amyloid Formation

@article{citeulike:1281585, abstract = {Human insulin has long been known to form amyloid fibrils under given conditions. The molecular basis of insulin aggregation is relevant for modeling the amyloidogenesis process, which is involved in many pathologies, as well as for improving delivery systems, used for diabetes treatments. Insulin aggregation displays a wide variety of morphologies, from small oligomeric filaments to huge floccules, and therefore different specific processes are likely to be intertwined in the overall aggregation. In the present work, we studied the aggregation kinetics of human insulin at low pH and different temperatures and concentrations. The structure and the morphogenesis of aggregates on a wide range of length scales (from monomeric proteins to elongated fibrils and larger aggregates networks) have been monitored by using different experimental techniques: time-lapse atomic force microscopy (AFM), quasi-elastic light-scattering (QLS), small and large angle static light-scattering, thioflavin T fluorescence, and optical microscopy. Our experiments, along with the analysis of scattered intensity distribution, show that fibrillar aggregates grow following a thermally activated heterogeneous coagulation mechanism, which includes both tip-to-tip elongation and lateral thickening. Also, the association of fibrils into bundles and larger clusters (up to tens of microns) occurs simultaneously and is responsible for an effective lag-time.}, author = {Mauro, Manno and Craparo, Emanuela F. and Podesta, Alessandro and Bulone, Donatella and Carrotta, Rita and Martorana, Vincenzo and Tiana, Guido and San Biagio, Pier L. }, citeulike-article-id = {1281585}, journal = {Journal of Molecular Biology}, keywords = {amyloid, experiment, insulin}, month = {February}, number = {1}, pages = {258--274}, posted-at = {2007-05-07 08:51:35}, priority = {2}, title = {Kinetics of Different Processes in Human Insulin Amyloid Formation}, url = {http://www.sciencedirect.com/science/article/B6WK7-4M9HVT2-1/2/16c6d6d72aa8e8d7b3fa43c8dafe7ae0}, volume = {366}, year = {2007} }

TY - JOUR ID - citeulike:1281585 L3 - citeulike-article-id:1281585 TI - Kinetics of Different Processes in Human Insulin Amyloid Formation JF - Journal of Molecular Biology VL - 366 IS - 1 SP - 258 EP - 274 N2 - Human insulin has long been known to form amyloid fibrils under given conditions. The molecular basis of insulin aggregation is relevant for modeling the amyloidogenesis process, which is involved in many pathologies, as well as for improving delivery systems, used for diabetes treatments. Insulin aggregation displays a wide variety of morphologies, from small oligomeric filaments to huge floccules, and therefore different specific processes are likely to be intertwined in the overall aggregation. In the present work, we studied the aggregation kinetics of human insulin at low pH and different temperatures and concentrations. The structure and the morphogenesis of aggregates on a wide range of length scales (from monomeric proteins to elongated fibrils and larger aggregates networks) have been monitored by using different experimental techniques: time-lapse atomic force microscopy (AFM), quasi-elastic light-scattering (QLS), small and large angle static light-scattering, thioflavin T fluorescence, and optical microscopy. Our experiments, along with the analysis of scattered intensity distribution, show that fibrillar aggregates grow following a thermally activated heterogeneous coagulation mechanism, which includes both tip-to-tip elongation and lateral thickening. Also, the association of fibrils into bundles and larger clusters (up to tens of microns) occurs simultaneously and is responsible for an effective lag-time. KW - amyloid KW - experiment KW - insulin AU - Mauro, Manno AU - Craparo, Emanuela AU - Podesta, Alessandro AU - Bulone, Donatella AU - Carrotta, Rita AU - Martorana, Vincenzo AU - Tiana, Guido AU - San Biagio, Pier PY - 2007/02/09/ UR - http://www.sciencedirect.com/science/article/B6WK7-4M9HVT2-1/2/16c6d6d72aa8e8d7b3fa43c8dafe7ae0 ER -