Solid‐State Nanopore Characterization of Dendrimer‐Peptide Conjugates Across Defined Peptide Loadings

ABSTRACT Dendrimer‐peptide conjugates (DPCs) are multivalent soft materials whose biological and transport behaviors depend critically on peptide loading density, yet ensemble methods cannot resolve how incremental ligand changes affect nanoscale structure, mechanical compliance, and transport dynamics at the single‐particle level. Here, chemically tuned controlled dielectric breakdown solid‐state nanopores are employed to probe DPCs with defined peptide loadings (DPC10, DPC40, DPC60, and DPC100), using surface‐modified G7 PAMAM dendrimers as a reference scaffold. Voltage‐dependent analysis of capture rates, current blockades, dwell times, deformation metrics, and electrical charge deficit (ECD) scaling reveals distinct loading‐dependent electromechanical signatures with subpopulation resolution. DPC10 exhibits rigid and uniform translocation dynamics, whereas DPC40 shows pronounced configurational heterogeneity, manifested as clustered ECD‐dwell time distributions. At elevated biases, the more open DPC60 displays enhanced deformability and rapid transport, while densely packed DPC100 translocates more slowly with the strongest monotonic coupling between blockade depth and dwell time. These results establish a mechanistic link between ligand density, nanoscale deformability, and pore‐coupled transport dynamics, enabling label‐free discrimination of dendrimer‐peptide architectures that are indistinguishable by ensemble methods. Solid‐state nanopore sensing thus provides a multiparametric analytical framework for resolving subpopulation heterogeneity in soft multivalent nanomaterials.