Nucleotide-responsive gel tips for atomic force microscopy

A cantilever used for atomic force microscopy (AFM) is modified by an ultra-thin layer of polymeric gel so that the resulting tip can respond differently depending on the kind of nucleotides present in solution. A cross-linked poly((3-acrylamidopropyl)trimethylammonium-co-(3-acrylamido)phenylboronic acid) is grafted on the surface of ordinary AFM tips by in-situ polymerization. The thickness of a dried polymer layer is determined to be 8 nm. In pure water, the force–distance curves of the gel tip against a hydrophobic surface indicate that the gel layer is swelled. At pH 7 and higher, adenosine 5’-monophosphate (AMP) causes the gel to shrink and a strong adhesion to appear in the force curve whereas 2’-deoxyadenosine 5ʹmonophosphate (dAMP) hardly affects the gel layer other than a slight shrinkage. Lowering pH to 4.8 using acetate buffer brings the once shrunken gel back to a swelled state again. Production of cross-linking points by a cyclic ester linkage between the phenylboronic acid group and the ribose unit of AMP and the electrostatic interaction of the anionic phosphate group of AMP with the cationic ammonium groups as well as neutralization of ionizable groups contributes to shrinkage of the gel layer. Thus, the cis-diol recognition ability of boronic acids is implemented effectively to the nucleotide-responsive AFM tip.