Nanoscale Curvature-Facilitated Membrane Intercalation of Conjugated Oligoelectrolytes Revealed by Nanobar-Supported Lipid Bilayers.

Conjugated oligoelectrolytes (COEs) constitute a powerful toolbox for detecting and modulating cell membrane properties. The versatility in their molecular structural design enables fine-tuning of their membrane intercalating behaviors, ranging from membrane disruption for antimicrobial applications to membrane stabilization for cell labeling and biosensing. However, a detailed description of the intercalation mechanism is absent, despite efforts to understand the impact of charge density and hydrophobic core length on the membrane intercalation efficiency of COEs. A critical yet overlooked factor is membrane curvature, which has been shown to modulate the spatiotemporal organization of molecules on cell membranes. Here, we found that nanoscale curved membranes serve as "hotspots" for COE intercalation. Using designed nanobar arrays with a gradient geometry, we generated nanobar-supported lipid bilayers with predefined membrane curvatures. Curvature-correlated spatial enrichment of COEs was observed on nanobars with curved ends of 600 nm diameter or below in a time-dependent manner. Higher membrane curvature corresponded to a faster COE intercalation rate and higher equilibrium capacity. Comparing COEs with different chemical structures, those with shorter hydrophobic cores and lower charge densities promoted more curvature-guided membrane intercalation. Membranes with increased surface charges or more lipid packing defects further reinforced the curvature preference of the COEs. These results indicate that membrane curvature plays a significant role in the spatiotemporal modulation of COE-membrane intercalation, forming strategies for tailored molecular designs to target cellular membranes of different shapes.