On-chip detection of wild 3R, 4R and mutant 4R tau through kinesin-microtubule binding

We report the successful demonstration of an on-chip tau detection system based on the difference in landing rate and binding density of microtubules (MTs) on a kinesin surface. Tau detection device comprises of a MT reservoir, channel and collector region with an overhang structure. We assayed MTs decorated with three tau types in the kinesin coated device. Since the increase in fluorescence intensity (FI) at the collector regions reflected the type of tau decorated on MTs, thus by measuring the FI we were able to distinguish wild 3R, 4R and P301L mutant tau.

[1]  M. C. Tarhan,et al.  Detection of mutations in the binding domain of tau protein by kinesin-microtubule gliding assay , 2014, 2014 IEEE 27th International Conference on Micro Electro Mechanical Systems (MEMS).

[2]  V. Lee,et al.  Cell-to-cell transmission of pathogenic proteins in neurodegenerative diseases , 2014, Nature Medicine.

[3]  M. Wolfe The Role of Tau in Neurodegenerative Diseases and Its Potential as a Therapeutic Target , 2012, Scientifica.

[4]  T. Goldberg,et al.  MAPT isoforms: differential transcriptional profiles related to 3R and 4R splice variants. , 2011, Journal of Alzheimer's disease : JAD.

[5]  Amanda Carroll-Portillo,et al.  In vitro capture, transport, and detection of protein analytes using kinesin-based nanoharvesters. , 2009, Small.

[6]  Ashutosh Agarwal,et al.  A smart dust biosensor powered by kinesin motors. , 2009, Nature nanotechnology.

[7]  Hiroyuki Fujita,et al.  Simultaneous and bidirectional transport of kinesin‐coated microspheres and dynein‐coated microspheres on polarity‐oriented microtubules , 2008, Biotechnology and bioengineering.

[8]  Banahalli R Ratna,et al.  Toward single molecule detection of staphylococcal enterotoxin B: mobile sandwich immunoassay on gliding microtubules. , 2008, Analytical chemistry.

[9]  K. Kurabayashi,et al.  Self-contained, biomolecular motor-driven protein sorting and concentrating in an ultrasensitive microfluidic chip. , 2008, Nano letters.

[10]  Cees Dekker,et al.  Molecular Sorting by Electrical Steering of Microtubules in Kinesin-Coated Channels , 2006, Science.

[11]  Viola Vogel,et al.  Selective loading of kinesin-powered molecular shuttles with protein cargo and its application to biosensing. , 2006, Small.

[12]  Viola Vogel,et al.  Mechanisms of Microtubule Guiding on Microfabricated Kinesin-Coated Surfaces: Chemical and Topographic Surface Patterns , 2003 .

[13]  J. Lee,et al.  Preparation of tubulin from brain. , 1982, Methods in enzymology.

[14]  James C. Lee,et al.  [36] Preparation of tubulin from brain , 1982 .