It is of critical importance to examine carefully the potential adverse effects of engineered nanoparticles (NPs) on human health and environments. In the present study, we have investigated the disruption of cell membranes induced by amorphous silica NPs in erythrocytes, lymphocytes (Jurkat), malignant melanocytes (B16F10), and macrophages (J774.1); these four types of mammalian cells have distinctive characteristics in terms of nucleated/non-nucleated cells, adherent/non-adherent cells, endocytosis, and phagocytosis. The silica-induced membranolysis was examined by exposing these different cells to serum-free culture media containing the amorphous silica NPs of different diameters (28, 50, 55, 156, and 461 nm) under similar conditions. We investigated how the silica-induced membranolysis of the cells of different origins is influenced by the size and dose of the silica NPs. Additionally, the interaction forces of a silica microsphere with a living cell or a giant unilamellar vesicle composed of zwitterionic phosphatidylcholine lipids were measured by colloid-probe atomic force microcopy, whereby the affinities of silica surface for plasma membranes and protein-free phospholipid membranes were estimated. Possible mechanism of the silica-induced membranolysis was discussed. (C) 2014 The Society of Powder Technology Japan. Published by Elsevier B.V. and The Society of Powder Technology Japan. All rights reserved.