If Squeezed, a Camel Passes Through the Eye of a Needle: Voltage-Mediated Stretching of Dendrimers Facilitates Passage Through a Nanopore.

Herein, we report uni-molecular observations of electric potential- and electrolyte-dependent elasticity of poly(amidoamine) (PAMAM)-G1.5 dendrimers containing sodium carboxylate surface groups, using the electric field-assisted migration through the α-hemolysin nanopore (α-HL). Although at moderate transmembrane potentials the dendrimer (~ 2.5 nm in diameter) is sterically excluded from translocation across the constriction region of the nanopore (~ 1.5 nm in diameter), we found a threshold for its translocation that depends on both the electrolyte pH and ionic strength. We posit that the decreased repulsive intramolecular interactions among dendrimer's branches at low when compared to neutral pH, caused mainly by the protonation of surface groups on the dendrimer, determine a larger propensity of the dendrimer to collapse and deform. This in turns enables the dendrimer to adopt more favorably conformations that facilitate its optimal squeezing through the α-HL's constriction region at low pH, despite the fact that the estimated net force acting on it becomes approximately one order of magnitude lower than at neutral pH. Experiments performed in a low ionic strength buffer, which decreases Coulombic screening, enhance the intramolecular forces on the dendrimer and renders the dendrimer stiffer than in high ionic strength buffer, confirming the dendrimer elastic properties-dependent threshold for deformation inside the nanopore.