Label-free detection of amyloid growth with microcantilever sensors.

We present an approach for sensing protein aggregation using microcantilever systems. Results from both single cantilever experiments with internal reference and multicantilever array measurements with dedicated reference cantilevers are discussed. We show that in both cases protein aggregation on the sensor can be detected through associated changes in surface stress.

[1]  G. Stoney The Tension of Metallic Films Deposited by Electrolysis , 1909 .

[2]  Scott J. Hultgren,et al.  Role of Escherichia coli Curli Operons in Directing Amyloid Fiber Formation , 2002, Science.

[3]  Marilyne Sousa,et al.  Investigating the molecular mechanisms of in-plane mechanochemistry on cantilever arrays. , 2007, Journal of the American Chemical Society.

[4]  C. Dobson Protein folding and misfolding , 2003, Nature.

[5]  T. Thundat,et al.  Bioassay of prostate-specific antigen (PSA) using microcantilevers , 2001, Nature Biotechnology.

[6]  S. Manalis,et al.  Micromechanical detection of proteins using aptamer-based receptor molecules. , 2004, Analytical chemistry.

[7]  M. Pepys Pathogenesis, diagnosis and treatment of systemic amyloidosis. , 2001, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[8]  S. Balasubramanian,et al.  DNA molecular motor driven micromechanical cantilever arrays. , 2005, Journal of the American Chemical Society.

[9]  Kenjiro Ono,et al.  Kinetic modeling and determination of reaction constants of Alzheimer's beta-amyloid fibril extension and dissociation using surface plasmon resonance. , 2002, Biochemistry.

[10]  A. Aguzzi Understanding the diversity of prions , 2004, Nature Cell Biology.

[11]  H. Rothuizen,et al.  Translating biomolecular recognition into nanomechanics. , 2000, Science.

[12]  Martin Hegner,et al.  Label free analysis of transcription factors using microcantilever arrays. , 2006, Biosensors & bioelectronics.

[13]  James K. Gimzewski,et al.  Observation of a chemical reaction using a micromechanical sensor , 1994 .

[14]  M. Welland,et al.  Microcantilever-based biosensors , 2000, Ultramicroscopy.

[15]  H. Lang,et al.  Multiple label-free biodetection and quantitative DNA-binding assays on a nanomechanical cantilever array , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[16]  Wenmiao Shu,et al.  Kinetics and thermodynamics of amyloid formation from direct measurements of fluctuations in fibril mass , 2007, Proceedings of the National Academy of Sciences.

[17]  J. K. Gimzewski,et al.  Photothermal spectroscopy with femtojoule sensitivity using a micromechanical device , 1994, Nature.

[18]  Jonathan S. Weissman,et al.  The physical basis of how prion conformations determine strain phenotypes , 2006, Nature.

[19]  Wenmiao Shu,et al.  Investigation of biotin-streptavidin binding interactions using microcantilever sensors. , 2007, Biosensors & bioelectronics.

[20]  R. Wickner,et al.  [URE3] as an altered URE2 protein: evidence for a prion analog in Saccharomyces cerevisiae. , 1994, Science.

[21]  Thomas Thundat,et al.  Thermal and ambient-induced deflections of scanning force microscope cantilevers , 1994 .

[22]  Atanas V Koulov,et al.  Functional amyloid--from bacteria to humans. , 2007, Trends in biochemical sciences.

[23]  D. Otzen,et al.  Quartz crystal microbalance studies of multilayer glucagon fibrillation at the solid-liquid interface. , 2007, Biophysical journal.

[24]  H. Lang,et al.  A label-free immunosensor array using single-chain antibody fragments. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[25]  S. Lindquist,et al.  Structural insights into a yeast prion illuminate nucleation and strain diversity , 2005, Nature.

[26]  C. Dobson,et al.  Protein misfolding, functional amyloid, and human disease. , 2006, Annual review of biochemistry.

[27]  T. Okada,et al.  Development of aggregation inhibitors for amyloid‐β peptides and their evaluation by quartz‐crystal microbalance , 2007, Chemical biology & drug design.