Rachel McKendry

To investigate the fundamental nanomechanical forces generated at biochemical interfaces. To exploit the biomolecular forces for label-free cantilever biosensor and nanorobotic applications. To probe the interlay between mechanical devices and living cellular systems Contact details: Office: Lab 1 Room 3C6 Tel: +44 (0)20 7679 9995 Ext: 39995 Fax: +44 (0)20 7678 0595 Email: r.a.mckendryucl.ac.uk

• Editorial Board of Royal Society of Chemistry Journal ‘The Analyst’

• London Centre for Nanotechnology Lead Scientist on ‘Soft Matter’ SPM

Recent Publications

‘Multiple label-free biodetection and quantitative DNA binding assays on a nanomechanical cantilever array’
McKendry, R. A.;  Zhang, J.; Arntz, Y.; Strunz, T.; Hegner, M.; Lang, H-P.; Baller, M.K.; Certa, U.; Guntherodt, H-J & Gerber, Ch.  Proc. Natl. Acad Sci. U.S.A.  99, 9783-9788 (2002).

Microarray technology is now an essential tool in genomics, proteomics and drug discovery. However most current methods rely on sample ;abelling, which is expensive, time-consuming and can potentially perturb the properties of the biomolecule under investigation. In this paper we report a microarray of miniaturized cantilevers to nanomechanically detect multiple unlabeled biomolecules simultaneously, at nanomolar concentrations and within minutes.

 
‘DNA molecular motor driven micromechanical Cantilever Arrays’
Shu, W.; Lui, D.; Watari, M.; Strunz, T.; Riener, C. ; Welland, M. E.;Balasubramanian, S. &  McKendry,   R. A. J. Am. Chem. Soc. 127, 17054-17060 (2005)

The unique ability of living systems to translate biochemical reactions into mechanical work has inspired the design of synthetic DNA motors which generate nanoscale motion via controlled conformational change. Here we report the direct integration between an ensemble of non-classical DNA i-motif motors and an array of microfabricated silicon cantilevers.  Hybrid devices which directly harness the multiple accessible conformational states of dynamic oligonucleotides and aptamers, translating biochemical energy into micromechanical work present a radical new approach to the construction of ‘smart’ nano-scale machinery and mechano-biosensors.

Rapid and label-free nanomechanical detection of biomarker transcripts in human RNA.’
Zhang, J.; Lang, HP.; Huber, F.; Bietsch, A.; Grange, W.; Certa, U.; McKendry, R.; Guntherodt, HJ.; Hegner, M. & Gerber, Ch.  Nature Nanotechnology, 1, 214-220 (2006).

We report the nanomechanical detection of mRNA biomarkers in total cellular RNA. Differential gene expression of the gene 1-8U, a potential marker for cancer progression or viral infections, has been observed in a complex background. The cantilever measurements provide results within minutes at the picomolar level without target amplification, and are sensitive to base mismatches. This qualifies the technology as a rapid method to validate biomarkers that reveal disease risk, disease progression or therapy response.

 
‘Investigating the Molecular Mechanisms of In-Plane Mechanochemistry on Cantilever Arrays.’
Watari, M.; Galbraith, J.; Lang, HP.; Sousa, M.; Hegner, M.; Gerber, C.; Horton, M. A. &  McKendry, R.A.  J. Am. Chem. Soc. accepted (2006)

In this paper we report a detailed study into the molecular basis of stress generation in aqueous environments focusing on the pH titration of model mercaptohexadecanoic acid self-assembled monolayers (SAMs). In-plane force titrations were found to have the sensitivity to detect ionic hydrogen bond formation between protonated and non-protonated carboxylic acid groups in the proximity of the surface pK_1/2. However striking differences were observed in the micromechanical responses to different ionic strength and ion species present in the aqueous environment, highlighting the critical role of counter- and co-ions on surface stress.

Main Biography

Professional Appointment

Education

Figure 1: Harnessing duplex-quadruplex conformation changes on a micromechanical cantilever array; a) i-motif structure; b) cantilever array; c) cantilever functionalized with duplex DNA; d) triggered by addition of protons the duplex to i-motif conformational change is translated into nanomechanical work. Reference: Shu et al J. Am. Chem. Soc. 127, 17054-17060 (2005).

Figure 2: Micromechanical manipulation of cellular shape; a) schematic diagram to show the principle of soft-lithography with fibronectin proteins; b) optical and fluorescent image of fibronectin/BSA protein arrays; c) Optical image of normal HELA cells; d) cell adhesion to the fibronectin pattern generates a ‘square’ HELA cell (Watari & McKendry, unpublished)