Direct tracking of amyloid and Tau dynamics in neuroblastoma cells using nanoplasmonic fiber tip probes
RJF Qimin Quan and Research Fellow Feng Liang in collaboration with Zhongcong Xie's MGH research group advance the efforts against Alzheimers with their break-through measurements of proteins within living cells. See MGH press release.
Amyloid plaques and neurofibrillary tangles are the pathological hallmarks of Alzheimer's disease. However, there has been a long standing debate 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 hours. 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.