Experimental and theoretical investigation of chain length and surface coverage on fouling of surface grafted polypeptoids.

Numerous strategies exist to prevent biological fouling of surfaces in physiological environments; our strategy focuses on the modification of surfaces with poly-N-substituted glycine oligomers (polypeptoids). We previously reported the synthesis and characterization of three novel polypeptoid polymers that can be used to modify titanium oxide surfaces, rendering the surfaces resistant to adsorption of proteins, to adhesion of mammalian and bacterial cells and to degradation by common protease enzymes. In this study, we investigated the effect of polypeptoid chain length on the antifouling properties of the modified surfaces. For these experiments we used poly(N-methoxyethyl) glycines with lengths between ten and fifty repeat units and determined the influence of chain length on coating thickness and density as well as resistance to protein adsorption and cellular adhesion. Short-term protein resistance remained low for all polymers, as measured by optical waveguide lightmode spectroscopy, while fibroblast adhesion after several weeks indicated reduced fouling resistance for the polypeptoid-modified surfaces with the shortest chain length polymer. Experimental observations were compared to predictions obtained from a molecular theory of polymer and protein adsorption. Good agreement was found between experiment and theory for the chain length dependence of peptoid grafting density, and for protein adsorption as a function of peptoid grafting density. The theoretical predictions provide specific guidelines for the surface coverage for each molecular weight for optimal antifouling. The predictions show the relationship between polymer layer structure and fouling.

Surface-immobilised antimicrobial peptoids.

Surface modification techniques that create surfaces capable of killing adherent bacteria are promising solutions to infections associated with implantable medical devices. Antimicrobial (AM) peptoid oligomers (ampetoids) that were designed to mimic helical AM peptides were synthesised with a peptoid spacer chain to allow mobility and an adhesive peptide moiety for easy and robust immobilisation onto substrata. TiO(2) substrata were modified with the ampetoids and subsequently backfilled with an antifouling (AF) polypeptoid polymer in order to create polymer surface coatings composed of both AM (active) and AF (passive) peptoid functionalities. Confocal microscopy images showed that the membranes of adherent E. coli cells were damaged after 2-h exposure to the modified substrata, suggesting that ampetoids retain AM properties even when immobilised on substrata.

Protein, cell and bacterial fouling resistance of polypeptoid-modified surfaces: effect of side-chain chemistry.

Peptidomimetic polymers consisting of poly-N-substituted glycine oligomers (polypeptoids) conjugated to biomimetic adhesive polypeptides were investigated as antifouling surface coatings. The polymers were immobilized onto TiO(2) surfaces via an anchoring peptide consisting of alternating residues of 3,4-dihydroxyphenylalanine (DOPA) and lysine. Three polypeptoid side-chain compositions were investigated for antifouling performance and stability toward enzymatic degradation. Ellipsometry and XPS analysis confirmed that purified polymers adsorbed strongly to TiO(2) surfaces, and the immobilized polymers were resistant to enzymatic degradation as demonstrated by mass spectrometry. All polypeptoid-modified surfaces exhibited significant reductions in adsorption of lysozyme, fibrinogen and serum proteins, and were resistant to 3T3 fibroblast cell attachment for up to seven days. Long-term in vitro cell attachment studies conducted for six weeks revealed the importance of polypeptoid side-chain composition, with a methoxyethyl side chain providing superior long-term fouling resistance compared to hydroxyethyl and hydroxypropyl side chains. Finally, attachment of both gram-positive and gram-negative bacteria for up to four days under continuous-flow conditions was significantly reduced on the polypeptoid-modified surfaces compared to unmodified TiO(2) surfaces. The results reveal the influence of polypeptoid side-chain chemistry on short-term and long-term protein, cell and bacterial fouling resistance.

New peptidomimetic polymers for antifouling surfaces.

Exposure of therapeutic and diagnostic medical devices to biological fluids is often accompanied by interfacial adsorption of proteins, cells, and microorganisms. Biofouling of surfaces can lead to compromised device performance or increased cost and in some cases may be life-threatening to the patient. Although numerous antifouling polymer coatings have enjoyed short-term success in preventing protein and cell adsorption on surfaces, none have proven ideal for conferring long-term biofouling resistance. Here we describe a new biomimetic antifouling N-substituted glycine polymer (peptoid) containing a C-terminal peptide anchor derived from residues found in mussel adhesive proteins for robust attachment of the polymer onto surfaces. The methoxyethyl side chain of the peptoid portion of the polymer was chosen for its chemical resemblance to the repeat unit of the known antifouling polymer poly(ethylene glycol) (PEG), whereas the composition of the 5-mer anchoring peptide was chosen to directly mimic the DOPA- and Lys-rich sequence of a known mussel adhesive protein. Surfaces modified with this biomimetic peptide-peptoid conjugate exhibited dramatic reduction of serum protein adsorption and resistance to mammalian cell attachment for over 5 months in an in vitro assay. These new synthetic peptide based antifouling polymers may provide long-term control of surface biofouling in the physiologic, marine, and industrial environments.