The manipulation of biological substrates is becoming more popular route toward generating novel computing devices. Physarum polycephalum is used as a model organism in biocomputing because it can create “wires” for use in hybrid circuits; programmable growth by manipulation through external stimuli and the ability withstanding a current and its tolerance to hybridization with a variety of nano/microparticles. Lettuce seedlings have also had previous interest invested in them for generating plant wires, although currently there is little information as to their suitability for such applications. In this study both P. polycephalum and Lettuce seedlings were hybridized with gold nanoparticles — functionalized and unfunctionalized — to explore their uptake, toxicological effects and, crucially, any alterations in electrical properties they bestow upon the organisms. Using various microscopy techniques it was shown that P. polycephalum and lettuce seedlings are able to internalize nanoparticles and assemble them in vivo, however some toxicological effects were observed. The electrical resistance of both lettuce seedlings and P. polycephalum was found to decrease, the most significant reduction being with lettuce seedlings whose resistance reduced from 3MΩΩs to 0.5MΩΩs. We conclude that gold is a suitable nanomaterial for biohybridization specifically in creating conductive pathways for more efficient biological wires in self-growing hybrid circuitry.