Controlling biological interfaces on the nanometer length scale

A number of techniques currently exist that allow researchers to generate spatially resolved patterns of chemistry and topography on the nanometer length scale. Both chemically and topographically nanopatterned surfaces can be generated to more accurately mimic the natural extracellular environment. Chemically patterned surfaces can also be used to study tightly controlled and highly specific cell-cell and cell-substrate interactions or to create increasingly densely packed biosensors. From a biological standpoint, these methods enable fabrication of elaborate interfaces to mechanistically study the effects of cell adhesion ligand density, spacing, clustering, and spatial distribution on cell fate and function. The most commonly used nanopatterning techniques in the biomaterials arena are reviewed here, including scanning probe, electron beam, colloidal, and imprint lithographies, critically examining the resolution available and the scalability of the technique for generating the number of surfaces necessary for statistically relevant cell culture studies.