Toxicity assessment of titanium dioxide nanoparticles on microorganisms through topological data analysis of high dimensional single-cell nanomechanical data.

There is a growing interest in the development of methods for the detection of nanoparticle (NP) toxicity to living organisms based on the analysis of relevant multidimensional data sets. In particular the detection of preliminary signs of NPs toxicity effects would benefit from the selection of data featuring NPs-induced alterations of biological barriers. Accordingly, we present an original Topological Data Analysis (TDA) of the nanomechanical properties of Escherichia coli cell surface, evaluated by multiparametric Atomic Force Microscopy (AFM) after exposure of the cells to increasing concentrations of titanium dioxide nanoparticles (TiONPs). Topological networks are generated from spatially resolved multidimensional nanomechanical cell data consisting of elastic moduli, turgor pressures and AFM tip indentations of the biosurface. The topological networks reflect the resistance/sensitivity of cells to TiONPs as a function of cell surface phenotype, and the methodology further highlights heterogeneities in response at the single cell and multi-individual levels. Overall, the method provides an efficient approach to assess nanoparticle toxicity without requiring prior knowledge, while naturally accounting for variability in cellular response at different scales.