The central goal of our proposal is to develop physically justified models and computational tools to quantitatively describe and understand the molecular mechanisms of nanoparticle-cell membrane interactions, which we consider to be a crucial point in any predictive model of nanoparticle toxicity. We consider mechanisms of nanoparticle protein corona formation, the protective function of the membrane, nanoparticle uptake into the cell, and the effect of nanoparticles on the cell membrane. We plan to develop a consistent multiscale simulation scheme starting from nanoparticle-biomolecule interaction at the atomistic scale using molecular dynamics simulation, and then systematically constructing coarse-grained mesoscale models for simulating the structure and dynamics of the cell membrane perturbed by nanoparticles at the physiologically relevant time and length scales. We will develop and test a universal method for evaluating the rates of nanoparticle translocation through membranes and evaluate associated specific toxicity effects. Based on the information acquired from the simulations and analyzed together with available experimental data, the toxicological impact will be deduced. We will apply our approach to a range of common engineered nanoparticles, relating their physicochemical properties such as size and shape, surface charge, hydrophobicity (logP), and plasma protein binding affinity to the toxicological effects and develop a test suite allowing to make toxicity prediction on the basis of purely computational or limited in vitro screening tests.