Length-Dependent Manifestation of Vibration Modes Regulates a Specific Intermediate Morphology of A17-42 in Different Environments

Abstract

Various cytotoxic mechanisms for neurodegenerative disease are induced by specific conformations of A intermediates. The efforts to understand the diverse intermediate forms of amyloid oligomers have been focused on understanding the aggregation mechanism of specific morphologies for A intermediates. However, these are still not easy tasks to be accomplished because the diverse conformations of A intermediates can be altered during the aggregation process, even though the same A monomers are present. Thus, efforts to reveal the conformational change mechanism could be a fundamental process to understand the formation of diverse A intermediate conformations. Here, we evaluate the conformational characteristics of A(17-42) fibrillar oligomers in different environments according to the length. We observed that A fibrillar oligomers optimize their inherent hydrogen bonds and configurational entropy to stabilize their structure according to the simulation time and their length increase. In addition, we revealed the role of the expressed vibration mode shape in the fibrillar oligomers elongation and deformation processes. Our results suggest that limitations in amyloid oligomer growth and transformations of their morphologies can be regulated and controlled by modifying the vibration features.