Nano- and microparticles of various shapes have recently been introduced for various drug-delivery applications. Shape of particles has been shown to have an impact on various processes including circulation, vascular adhesion and phagocytosis. Here, we assess the role of particle geometry and surface chemistry in their interactions with cell membranes. Using representative particles of different shape (spheres, elongated and flat particles), size (500 nm-1 microm) and surface chemistry (positively and negatively charged), we evaluated the response of endothelial cells to particles. While spherical and elliptical disc-shaped particles did not have an impact on cell spreading and motility, needle-shaped particles induced significant changes in the same. Further studies revealed that needle-shaped particles induced disruption of cell membranes as indicated by the release of lactate dehydrogenase and uptake of extracellular calcein. The effect of needle-shaped particles on cells was transient and was reversed over a time period of 1-48 h depending on particle parameters.