Chemical Force Microscopy

–Probing the Biologically Important Receptors by AFM–

[Funding sources] SNF, University of Pennsylvania Nano-Bio Interface Center (NSF)

[Collaborators] Prof. Dr. Nicholas D. Spencer (ETH), Prof. Dr. Robert W. Carpick (University of Pennsylvania), Prof. Dr. Helen Hansma (UC Santa Barbara), Prof. Dr. Ken-ichi Fukui (Osaka University)

1. Single molecular detection of ligand-receptor interaction

Many biologically important proteins are transmembrane receptors, which are difficult to express in quantity and to crystalize. AFM analysis, which is also amenable to the measurements under physiological condition, is an ideal way of mechanism analyses such transmembrane receptors.  Unique molecular tripods were synthesized to successfully observe  single molecular ligand–receptor interactions. In addition to the Au-coated AFM tips, nano-crystalline diamond (NCD) AFM tips were used addressing super-robust chemical tips.

Publications: Langmuir 2010, J. Mat. Chem. 2012.

2. Analyses of transmembrane receptors

A recombinant of P2X2 receptor, transmembrane ATP receptor involved in pain transmission, was prepared and immobilized on mica surface. AFM imaging in solution revealed a channel-like structure ,suggesting the protein formed 3D structures on surface. Further efforts using other transmembrane receptors are currently going on.

Publications: Eur. J. Pharmacol. 2005, Nanoscale 2015.

3. Photoswitchable molecular tripod

In order to realize a simultaneous bifunctional AFM imaging (topography and chemical identification), a unique photo-switchable molecular tripod was designed and synthesized. The molecule remained stably attached to the gold surface and showed  reversible photoinduced E and isomerization as observed by UHV-NC-AFM.

Publications: J. Phys. Chem. B 2006, Org. Biomol. Chem. 2010.

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