Peptides carry enormous capacity and versatility for participating in specific ligand-receptor binding interactions. As small fragments of proteins, they offer the possibility of delivering a selected activity in constructing a biofunctionalized surface or interface, absent other, undesired activities present in the full protein molecule (e.g., immunogenicity). We have been exploring the self-assembly and cell recognition properties of peptide fragments (thus far derived from extracellular matrix fragments) that we have lipidated synthetically by attaching a phospholipid-mimic, double-chain, hydrocarbon tail. Lipidation confers interesting amphiphilic and self-organization properties on the molecules and enables the stable deposition of layers of peptide amphiphiles on surfaces. Specifically, we have been using peptide amphiphiles to functionalize surfaces with peptide fragments derived from collagen and fibronectin. Deposition of these molecules by Langmuir-Blodgett methods gives a very high degree of control over the density and orientation of the surface molecules. This in turn enables us explore the effects on cell response of peptide density and molecular architecture variations with a great degree of precision. The principal results so far, which seem to have some generality for different kinds of peptides, are that there is an optimum peptide density for each kind of peptide fragment, and that the architecture of peptide presentation is a very sensitive controller of bioactivity. Examples will be given of these effects.