HypothesisNanomaterials have been extensively investigated for a wide range of biomedical applications, including as antimicrobial agents, drug delivery vehicles, and diagnostic devices. The commonality between these biomedical applications is the necessity for the nanoparticle to interact with or pass through the cellular wall and membrane. Cell-nanomaterial interactions/uptake can occur in various ways, including adhering to the cell wall, forming aggregates on the surface, becoming absorbed within the cell wall itself, or transversing into the cell cytoplasm. These interactions are common to mammalian cells, bacteria, and yeast cells. This variety of interactions can cause changes to the integrity of the cell wall and the cell overall, but the precise mechanisms underpinning such interactions remain poorly understood. Here, we investigate the interaction between commonly investigated gold nanoparticles (AuNPs) and the cell wall/membrane of a model fungal cell to explore the general effects of interaction and uptake. ExperimentsThe interactions between 100 nm citrate-capped AuNPs and the cell wall of Candida albicans fungal cells were studied using a range of advanced microscopy techniques, including atomic force microscopy, confocal laser scanning microscopy, scanning electron microscopy, transmission electron microscopy, and synchrotron-FTIR micro-spectroscopy. FindingsIn most cases, particles adhered on the cell surface, although instances of particles being up-taken into the cell cytoplasm and localised within the cell wall and membrane were also observed. There was a measurable increase in the stiffness of the fungal cell after AuNPs were introduced. Analysis of the synchrotron-FTIR data showed significant changes in spectral features associated with phospholipids and proteins after exposure to AuNPs.