Hydration shells of normal proteins display regions of highly structured water as well as patches of less structured bulk-like water. Recent studies suggest that isomers with larger surface densities of patches of bulk-like water have an increased propensity to aggregate. These aggregates are toxic to the cellular environment. Hence, the early detection of these toxic deposits is of paramount medical importance. We show that various morphological states of association of such isomers can be differentiated from the normal protein background based on the characteristic partition between bulk, caged, and surface hydration water and the magnetic resonance (MR) signals of this water. We derive simple mathematical equations relating the compartmentalization of water to the local hydration fraction and the packing density of the newly formed molecular assemblies. Then, we employ these equations to predict the MR response of water constrained by protein aggregation. Our results indicate that single units and compact aggregates that contain no water between constituents induce a shift of the MR signal from normal protein background to values in the hyperintensity domain (bright spots), corresponding to bulk water. In contrast, large plaques that cage significant amounts of water between constituents are likely to generate MR responses in the hypointensity domain (dark spots), typical for strongly correlated water. The implication of these results is that amyloids can display both dark and bright spots when compared to the normal gray background tissue on MR images. In addition, our findings predict that the bright spots are more likely to correspond to amyloids in their early stage of development. The results help explain the MR contrast patterns of amyloids and suggest a new approach for identifying unusual protein aggregation related to disease.

中文翻译：

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淀粉样蛋白分子结构的水合曲线

正常蛋白质的水合壳显示出高度结构化的水区域以及结构化程度较低的块状水。最近的研究表明，具有较大表面密度的块状水块的异构体具有增加的聚集倾向。这些聚集体对细胞环境有毒。因此，及早发现这些有毒沉积物具有至关重要的医学意义。我们表明，基于散装、笼状和表面水合水之间的特征分区以及这种水的磁共振 (MR) 信号，可以将此类异构体的各种形态学状态与正常蛋白质背景区分开来。我们推导出简单的数学方程，将水的划分与局部水合分数和新形成的分子组件的堆积密度相关联。然后，我们使用这些方程来预测受蛋白质聚集约束的水的 MR 响应。我们的结果表明，在成分之间不包含水的单个单元和致密聚集体会导致 MR 信号从正常蛋白质背景转移到与大量水相对应的高强度域（亮点）中的值。相比之下，在成分之间包含大量水的大斑块可能会在低强度域（黑点）中产生 MR 响应，这对于强相关水是典型的。这些结果的含义是，与 MR 图像上的正常灰色背景组织相比，淀粉样蛋白可以同时显示暗点和亮点。此外，我们的研究结果预测亮点更可能对应于早期发育阶段的淀粉样蛋白。结果有助于解释淀粉样蛋白的 MR 对比模式，并提出了一种识别与疾病相关的异常蛋白质聚集的新方法。