Direct Tracking of Amyloid and Tu Dynamics in Neuroblastoma Cells Using Nanoplasmonic Fiber Tip Probes.
Amyloid plaques and neurofibrillary tangles are the pathological hallmarks of Alzheimer's disease. However, there has been a long-standing discussion on the dynamic relations between Aβ and tau proteins, partially due to the lack of a tool to track protein dynamics in individual live neurons at the early stage of Aβ generation and tau phosphorylation. Here, we developed nanoplasmonic fiber tip probe (nFTP) technology to simultaneously monitor Aβ42 generation and tau phosphorylation (at serine 262) in living, single neuroblastoma cells over 12 h. We observed that Aβ42 generation, under clinically relevant anesthetic treatment, preceded tau phosphorylation, which then facilitated Aβ42 generation. This observation is also supported by measuring proteins in cell lysates using the ultrasensitive label-free photonic crystal nanosensors. nFTP therefore provides an advanced method to investigate protein expression and post-translational modification in live cells and determine outcomes of intervention of Alzheimer's disease and other neurodegenerative disorders.
Rowland Institute at Harvard University , Cambridge, Massachusetts 02142, United States.
Feng
F
Liang
Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, United States.
Yiying
Y
Zhang
Rowland Institute at Harvard University , Cambridge, Massachusetts 02142, United States.|Department of Chemistry and Chemical Biology, Harvard University , Cambridge, Massachusetts 02138, United States.
Wooyoung
W
Hong
Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, United States.
Yuanlin
Y
Dong
Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, United States.
Zhongcong
Z
Xie
Rowland Institute at Harvard University , Cambridge, Massachusetts 02142, United States.
Qimin
Q
Quan
D000544:Alzheimer Disease; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D045744:Cell Line, Tumor; D006801:Humans; D036103:Nanotechnology; D009447:Neuroblastoma / Q000737:chemistry*; D010766:Phosphorylation; D016875:tau Proteins / Q000737:chemistry*
D016229:Amyloid beta-Peptides; D016875:tau Proteins
Alzheimer’s disease; Aβ; nanoplasmonic fiber tip probe (nFTP); photonic crystal nanosensor; protein dynamics; tau