Upper left: untreated. Lower right: treated. Image courtesy of Phillip B. Messersmith.

The "bio-inspired" mimics create "nonfouling" surfaces, which are resistant to protein and cellular growth. "Ours is the first report of the use of mussel adhesive mimics to prepare nonfouling surfaces," Phillip Messersmith, assistant professor of biomedical engineering at Northwestern University, told BioMedNet News.

Mussel adhesive proteins (MAPs) form a type of underwater glue that tethers marine organisms to their substrates. Secreted as fluids, MAPs undergo a crosslinking or hardening reaction to form a solid adhesive plaque. MAP plaques cure in situ to form tenacious, water-resistant bonds.

Both the adhesion and crosslinking characteristics of MAPs are attributed to forms of the amino acid L-3,4- dihydroxyphenylalanine (DOPA). Oxidation of DOPA to the o-quinone form induces crosslinking, whereas the catechol form of DOPA is thought to spur substrate adhesion.

To make their synthetic polymers, Messersmith and his team couple DOPA anchor residues to biocompatible water-soluble polymers, such as polyethylene glycol (PEG), using bioconjugate chemistry. Branched versions of these polymers are rapidly crosslinked into rigid PEG-based hydrogels, which may be useful for drug delivery and tissue engineering applications.

Messersmith's synthetic polymers take three major forms.

PEG-anchored by DOPA onto metal, metal oxide and semiconductor nanoparticle surfaces render nanoparticles resistant to aggregation under physiologic conditions. These polymers are ideally suited for medical applications: They can tolerate a range of physiologic conditions such as high salt environments, resist agglomeration, and permit minimally invasive drug delivery.

A second application, PEG anchored by DOPA onto gold substrate, creates nonfouling surfaces that limit protein adsorption and inhibit nonspecific cell adhesion and spreading.

In experiments comparing treated (nonfouling) to untreated (fouling) surfaces, monolayers of NIH 3T3 cells are almost completely eliminated on nonfouling surfaces after incubation for 4 hours at 37°C. Protein- and cell-resistant, the nonfouling surfaces are ideal candidates for biosensor and medical implant applications.

Finally, DOPA-modified block copolymers exhibit enhanced adhesion to glass surfaces. With hydrophobic cores and hydrophilic ends, copolymers self-assemble in water to form block copolymers; a block of 50 such nanoparticles is 10-50 nm in diameter.

Messersmith expects the research to have significant impact on nanoparticle-based therapeutics, imaging agents, medical devices, and biosensors. "Like other groups," he said, "we are certainly interested in making adhesive biomaterials for tissue adhesives and drug delivery."