Decoupling competing surface binding kinetics and reconfiguration of receptor footprint for ultrasensitive stress assays

Decoupling competing surface binding kinetics and reconfiguration of receptor footprint for ultrasensitive stress assays

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ABSTRACT Cantilever arrays have been used to monitor biochemical interactions and their associated stress. However, it is often necessary to passivate the underside of the cantilever to


prevent unwanted ligand adsorption, and this process requires tedious optimization. Here, we show a way to immobilize membrane receptors on nanomechanical cantilevers so that they can


function without passivating the underlying surface. Using equilibrium theory, we quantitatively describe the mechanical responses of vancomycin, human immunodeficiency virus type 1 antigens


and coagulation factor VIII captured on the cantilever in the presence of competing stresses from the top and bottom cantilever surfaces. We show that the area per receptor molecule on the


cantilever surface influences ligand–receptor binding and plays an important role on stress. Our results offer a new way to sense biomolecules and will aid in the creation of ultrasensitive


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of native HIV-1 gp120 trimers. _Nature_ 455, 109–113 (2008). Article  CAS  Google Scholar  Download references ACKNOWLEDGEMENTS We thank the EPSRC Grand Challenge in Nanotechnology for


Healthcare (EP/G0620064/1), I-sense EPSRC IRC in Early Warning Sensing Systems for Infectious Diseases (EP/G062064/1), Royal Society (RS), Targanta Therapeutics, Bio Nano Consulting (BNC),


the European Union FP7 Project VSMMART Nano (managed by BNC) for funding. The authors also thank J. Russat (London Centre for Nanotechnology), S. Sivachelvam (London Centre for


Nanotechnology), M. Rehak (Sphere Fluidics, UK), R.A. Weiss (University College London) C.T. Verrips (QVQuality, Utrecht), T. Philips (Utrecht University), M. Morfini (University of


Florence), T. Cass (Imperial College), V. Emery (Surrey Business School) and G. Aeppli (Paul Scherrer Institut) for the kind gift of materials and for helpful discussions. The glycoprotein


antigens (gp140CN54 and gp140UG37) to llama antibody fragments were provided by the Centre for AIDS Reagents, National Institute for Biological Standards and Control (NIBSC) of the UK


Medicines & Healthcare Products Regulatory Agency (MHRA). AUTHOR INFORMATION Author notes * Samadhan B. Patil, Manuel Vögtli, Benjamin Webb and Joseph W. Ndieyira: These authors


contributed equally to this work AUTHORS AND AFFILIATIONS * London Centre for Nanotechnology and Departments of Medicine and Physics, University College London, 17–19 Gordon Street, London,


WC1H 0AH, UK Samadhan B. Patil, Manuel Vögtli, Benjamin Webb, Rachel A. McKendry & Joseph W. Ndieyira * Department of Materials, Imperial College London, London, SW7 2AZ, UK Samadhan B.


Patil & Yeong-Ah Soh * Division of Infection & Immunity, University College London, Cruciform Building, Gower Street, London, WC1E 6BT, UK Benjamin Webb * UCL Institute for Liver and


Digestive Health, Royal Free Hospital, London, NW3 2QG, UK Giuseppe Mazza & Massimo Pinzani * Department of Chemistry, Jomo Kenyatta University of Agriculture and Technology, Nairobi,


PO Box 62000, Kenya Joseph W. Ndieyira Authors * Samadhan B. Patil View author publications You can also search for this author inPubMed Google Scholar * Manuel Vögtli View author


publications You can also search for this author inPubMed Google Scholar * Benjamin Webb View author publications You can also search for this author inPubMed Google Scholar * Giuseppe Mazza


View author publications You can also search for this author inPubMed Google Scholar * Massimo Pinzani View author publications You can also search for this author inPubMed Google Scholar *


Yeong-Ah Soh View author publications You can also search for this author inPubMed Google Scholar * Rachel A. McKendry View author publications You can also search for this author inPubMed 


Google Scholar * Joseph W. Ndieyira View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS J.W.N. designed the experiments. J.W.N. and M.V.


performed the experiments on antibiotics. J.W.N., S.B.P. and B.W. performed the experiments on HIV antigen detections. J.W.N. and S.B.P. formulated the mathematical model to decouple


competing surface binding kinetics at Au (top surface of cantilever) and Si (bottom surface of cantilever). J.W.N. performed the experiments on blood clotting proteins and wrote the paper.


All authors discussed the results and commented on the manuscript. CORRESPONDING AUTHOR Correspondence to Joseph W. Ndieyira. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no


competing financial interests. SUPPLEMENTARY INFORMATION SUPPLEMENTARY INFORMATION Supplementary information (PDF 452 kb) RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE


CITE THIS ARTICLE Patil, S., Vögtli, M., Webb, B. _et al._ Decoupling competing surface binding kinetics and reconfiguration of receptor footprint for ultrasensitive stress assays. _Nature


Nanotech_ 10, 899–907 (2015). https://doi.org/10.1038/nnano.2015.174 Download citation * Received: 15 November 2014 * Accepted: 06 July 2015 * Published: 17 August 2015 * Issue Date: October


2015 * DOI: https://doi.org/10.1038/nnano.2015.174 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link


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