FORCE MICROSCOPY OF ABETA & ALPHA SYNUCLEIN AGGREGATION

大脑中含有纤维化形式的Abeta和α-突触核蛋白的异常蛋白质沉积是阿尔茨海默病和帕金森病的特征，它们可能在神经退化中发挥作用。对Abeta和α-突触核蛋白聚集机制的详细了解将有助于阐明疾病进展的步骤，潜在地确定治疗策略。这项拟议的研究将继续对Abeta进行扫描力显微镜(SFM)研究，并启动对α-突触核蛋白的类似研究。SFM研究将使用最近开发的碳纳米管尖端，它允许比以前获得的更高分辨率的成像。具有纳米管尖端的化学力显微镜(CFM)将被用来高分辨率地绘制蛋白质聚集体上的官能团分布。同时，纳米管尖端的进一步锐化将通过溅射和电化学刻蚀技术来进行。最终的目标是，在单个单壁纳米管中结束的尖端，应该在SFM和CFM中达到1-2 nm的分辨率，比标准的SFM尖端提高了一个数量级。这些超高分辨率的提示将被用来实现对Abeta和α-突触核蛋白聚集的分子尺度的理解。

Abnormal protein deposits in the brain which contain fibrilized forms of Abeta and alpha-synuclein proteins are characteristic of Alzheimer's Disease and Parkinson's Disease, and they may play a causative role in neurodegeneration. Detailed knowledge of the aggregation mechanisms of Abeta and alpha-synuclein would elucidate the steps in disease progression, potentially identifying therapeutic strategies. The proposed research will continue a scanning force microscopy (SFM) study of Abeta and initiate similar research on alpha-synuclein. The SFM studies will use recently developed carbon nanotube tips, which allow higher resolution imaging than previously attained. Chemical force microscopy (CFM) with nanotube tips will be used to map the functional group distribution on the protein aggregates with high resolution. Concurrently, the further sharpening of nanotube tips will be pursued by sputtering and electrochemical etching techniques. The ultimate goal, a tip which ends in an individual singe-walled nanotube, should achieve 1 - 2 nm resolution in SFM and CFM, an order of magnitude improvement over standard SFM tips. These ultrahigh resolution tips will be used to achieve a molecular scale understanding of Abeta and alpha-synuclein aggregation.