Single-molecule electrostatic imaging of biomolecular interactions

Abstract

Molecular biophysics is governed to a great degree by electrostatic interactions between biomolecules. In this project we will investigate the interaction between globular proteins and amyloid fibrils by single-molecule electrostatic imaging. As a particular example, we will investigate how electrostatic forces influence the aggregation between serum amyloid p component (SAP), a plasma protein resistant to proteolysis, and A-beta amyloid fibrils, which are the hallmark of Alzheimer’s Disease. To this end, we will employ and adapt Kelvin-probe Force Microscopy (KFM), a technique from Physics/Materials Sciences, which is now increasingly used in Molecular Biology due to its unsurpassed charge sensitivity. 

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References:
[1]

Leung, C., Maradan, D., Kramer, A., Howorka, S., Mesquida, P., & Hoogenboom, B. W. (2010). Improved Kelvin probe force microscopy for imaging individual DNA molecules on insulating surfaces. Applied Physics Letters, 97(20). 

[2]

Mesquida, P., Ammann, D. L., MacPhee, C. E., & McKendry, R. A. (2005). Microarrays of peptide fibrils created by electrostatically controlled deposition. Advanced Materials, 17(7), 893-+.

[3]

M.B.Pepys, …, S.P.Wood, “Targeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis”, NATURE 417:254-259, 2002

[4]

Leung, C., Kinns, H., Hoogenboom, B. W., Howorka, S., & Mesquida, P. (2009). Imaging Surface Charges of Individual Biomolecules. Nano Letters, 9(7), 2769-2773.


Biological Areas:

Structural Biology
Chemical Biology

BBSRC Area:

Genes, development and STEM approaches to biology
Molecules, cells and industrial biotechnology