Surface organization and nanopatterning of collagen by dip-pen nanolithography

Collagen is a key fibrous protein in biological systems, characterized by a complex structural hierarchy as well as the ability to self-assemble into liquid crystalline mesophases. The structural features of collagen influenc e cellular responses and material properties, with importance for a wide ra nge of biomaterials and tissue architectures. The mechanism by which fibril lar collagen structures form from liquid crystalline mesophases is not well characterized. We report positive printing of collagen and a collagen-like peptide down to 30-50-nm line widths, using the atomic force microscopy te chnique of dip-pen nanolithography. The method preserved the triple-helical structure and biological activity of collagen and even fostered the format ion of characteristic higher levels of structural organization. The "direct -write" capability of biologically relevant molecules, while preserving the ir structure and functionality, provides tremendous flexibility in future b iological device applications and in proteomics arrays, as well as anew str ategy to study the important hierarchical assembly processes of biological systems.