Nanoscale Investigation of Generation 1 PAMAM Dendrimers Interaction with a Protein Nanopore

Herein, we describe at uni-molecular level the interactions between poly( amidoamine) ( PAMAM) dendrimers of generation 1 and the alpha-hemolysin protein nanopore, at acidic and neutral pH, and ionic strengths of 0.5 M and 1 M KCl, via single-molecule electrical recordings. The results indicate that kinetics of dendrimer-alpha-hemolysin reversible interactions is faster at neutral as compared to acidic pH, and we propose as a putative explanation the fine interplay among conformational and rigidity changes on the dendrimer structure, and the ionization state of the dendrimer and the alpha-hemolysin. From the analysis of the dendrimer's residence time inside the nanopore, we posit that the pH-and salt-dependent, long-range electrostatic interactions experienced by the dendrimer inside the ion-selective alpha-hemolysin, induce a non-Stokesian diffusive behavior of the analyte inside the nanopore. We also show that the ability of dendrimer molecules to adapt their structure to nanoscopic spaces, and control the flow of matter through the alpha-hemolysin nanopore, depends non-trivially on the pH-and salt-induced conformational changes of the dendrimer.