Single polymer chains as specific transducers of molecular recognition in scanning probe microscopy

A new approach for the specific detection and mapping of single molecule recognition is presented, based on the nonlinear elastic behavior of a single polymer chain. The process of molecular recognition between a ligand and a receptor is inherently accompanied by a decrease in the translational and rotational degrees of freedom of the two molecules. We show that a polymeric tether linked to the ligand can effectively transduce the configurational constraint imposed by molecular recognition into a measurable force, which is dominated by the entropic elasticity of the polymer. This force is specifically characterized by a strong nonlinearity when the extension of the polymer approaches its contour length. Thus, a polymer chain tethering the ligand to an oscillating cantilevered tip gives rise to a highly anharmonic motion upon ligand-receptor binding. Higher-harmonics atomic force microscopy allows us to detect this phenomenon in real time as a specific signature for the probing and mapping of single-molecule recognition.