Poly (ethylene glycol) (PEG) is widely used in the pharmaceutical, biotechnology, and medical device industries. Although PEG is a biocompatible polymer that has enjoyed widespread use in drug delivery technology, it is not considered adhesive toward mucosal tissue. Here the authors describe a simple approach to enhancing mucoadsorption of PEG polymers through end group functionalization with the amino acid 3,4-dihydroxyphenyl-L-alanine (DOPA) . Using a variety of surface analytical techniques, the authors show that a four-armed poly(ethylene glycol) polymer functionalized with a single DOPA residue at the terminus of each arm (PEG-(DOPA)(4)) adsorbed strongly to surface immobilized mucin. Successful mucoadsorption of PEG-(DOPA)(4) across several pH values ranging from 4.5 to 8.5 was demonstrated, and control experiments with unfunctionalized four-arm PEG demonstrated that mucoadsorption of PEG-(DOPA)(4) is due largely to the presence of DOPA end groups. This conclusion was confirmed with single molecule atomic force microscopy experiments that revealed a surprisingly strong interaction force of 371 +/- 93 pN between DOPA and adsorbed mucin. Direct comparisons with known mucoadhesive polymers revealed that PEG(DOPA)(4) was equal to or more adsorptive to immobilized mucin than these existing mucoadhesive polymers. In addition to demonstrating significant enhancement of mucoadhesive properties of PEG by DOPA functionalization, this study also introduced a new simple approach for rapid screening of mucoadhesive polymers. (c) 2006 American Vacuum Society.