Nanostructures of different sizes, shapes and material properties have many applications in biomedical imaging, clinical diagnostics and therapeutics . In spite of what has been achieved so far, a complete understanding of how cells interact with nanostructures of well-defined sizes, at the molecular level, remains poorly understood. Here we show that gold and silver nanoparticles coated with antibodies can regulate the process of membrane receptor internalization. The binding and activation of membrane receptors and subsequent protein expression strongly depend on nanoparticle size. Although all nanoparticles within the 2 -100 nm size range were found to alter signalling processes essential for basic cell functions (including cell death) 7 , 40-and 50-nm nanoparticles demonstrated the greatest effect. These results show that nanoparticles should no longer be viewed as simple carriers for biomedical applications, but can also play an active role in mediating biological effects. The findings presented here may assist in the design of nanoscale delivery and therapeutic systems and provide insights into nanotoxicity.Cells control their function and state through numerous processes of intracellular signalling events that are normally triggered by the binding of a ligand molecule with cell surface receptors. The extent of receptor-ligand binding and receptor crosslinking affects the intensity and duration of intracellular signalling and other downstream events, such as those seen with the transmembrane receptor tyrosine kinases 8,9 . Ligands with multiple receptor binding sites, known as multivalent ligands, can crosslink the membrane receptors more efficiently to regulate signalling processes 10 . Nanoparticles coated with antibodies could potentially function as multivalent ligands that are capable of crosslinking surface receptors. By changing the size, shape and material properties of the engineered nanoparticles, the degree of receptor crosslinking and subsequent cell responses can be precisely controlled.Recent observations in biological systems suggest that the physical parameters of nanoparticles can affect their nonspecific uptake in cells, with potential to induce cellular responses . However, these studies provide limited information regarding the cellular processes involved in nanoparticle trafficking and their ensuing functional impact. The understanding of how engineered nanoparticles of different geometries interact with cells requires the study of the molecular events involved in nanoparticlemembrane receptor binding, endocytosis and subsequent signalling activation. The characterization of these molecular