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Amphiphilic Polybetaines: the Effect of Side-Chain Hydrophobicity on Protein Adsorption Semra Colak and Gregory N

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Amphiphilic Polybetaines: the Effect of Side-Chain Hydrophobicity on Protein Adsorption Semra Colak and Gregory N Communication pubs.acs.org/Biomac Amphiphilic Polybetaines: The Effect of Side-Chain Hydrophobicity on Protein Adsorption Semra Colak and Gregory N. Tew* Department of Polymer Science and Engineering, University of Massachusetts − Amherst, Conte Research Center for Polymers, 120 Governor’s Drive, Amherst, Massachusetts 01003, United States *S Supporting Information ABSTRACT: Novel amphiphilic polybetaines were synthe- sized and used as the base material for nonfouling coatings. The amphiphilicity of these polybetaines was systematically tuned by coupling chains of increasing hydrophobicity to the zwitterionic functionality side at the repeat unit level. An oligoethylene glycol (OEG) moiety was selected to yield the fl most hydrophilic coating, while octyl (C8) and uorinated (F) groups were used to impart lipophilicity and lipophobicity to the coatings, respectively. This unique design allowed us to investigate the effect of the lipophilicity/lipophobicity of the side chain on the nonfouling properties of these zwitterionic systems. Adsorption studies, performed using six different proteins, showed that the fluorinated polybetaine, Poly[NFZI- co-NSi], resisted nonspecific adsorption as effectively as, and in some cases even better than, the most hydrophilic Poly[NOEGZI-co-NSi] coating. The comparison of Poly[NFZI-co-NSi] to its noncharged analog demonstrated the essential nature of the zwitterionic functionality in imparting nonfouling character to the coating. ■ INTRODUCTION organisms, can restructure their surfaces depending on the 15,16 A unique series of amphiphilic betaine copolymers, designed to environment. fi explore the effect of increasing the hydrophobicity on the The rst example of an amphiphilic nonfouling material was nonfouling properties of surfaces, is introduced. Fouling studies reported by Wooley and coworkers, where hyperbranched fl showed that a zwitterionic surface with both hydrophobic and uoropolymers (HBFPs) were cross-linked with linear PEG chains to obtain coatings with complex surface morpholo- lipophobic properties resists protein adsorption as well as one 17,18 with only hydrophilic character. Biofilm formation on gies. Because of the incompatibility of the hydrophilic and substrates, caused by the attachment and growth of micro- hydrophobic domains, these coatings showed phase segrega- organisms in aqueous environments, is a ubiquitous problem tion, resulting in topological surface roughness when immersed that can lead to various adverse events.1 These include, but are in aqueous media. The nonfouling performance of these cross- not limited to, thrombosis, microbial infections, and reduction linked, amphiphilic networks was tested using various ffi 2 biomacromolecules with adhesion affinity to either hydrophilic in the e cacy/sensitivity of devices. A key challenge in 19 preventing biofilm formation is the design of smart materials or or hydrophobic substrates. The results showed that engineered surfaces that can effectively resist the irreversible independent of the adhesion preference of proteins and the − attachment of a wide variety of species including proteins, larger microorganisms tested, the amphiphilic coatings, HBFP − ff fi microbial cells, and spores.2 5 Among many approaches PEG, were more e ective in resisting nonspeci c adsorption investigated, hydrophilic modification of surfaces using poly- than the coatings composed of only HBFP or PEG. In a similar − (ethylene glycol) (PEG),4,6 8 and more recently, zwitterionic example, a surface-active block copolymer (SABC) was − polymers5,9 11 with high wettability were found to be among developed and used to prepare antifouling coatings by Ober 15,20−24 the most promising candidates. However, larger microorgan- and coworkers. The SABC was composed of a isms as well as proteins are inherently amphiphilic. They polystyrene block and a comb-like amphiphilic block, in fl operate by different attachment mechanisms, with some having which both PEG and uoroalkyl groups were on the same ff higher affinity to hydrophobic surfaces and others to hydro- side chain. The e ectiveness of these coatings was tested for 25 philic.12,13 Therefore, solely hydrophilic or hydrophobic resistance to bovine serum albumin (BSA) and marine algae surfaces are often inadequate in resisting fouling upon prolonged exposure to complex environments such as Received: January 4, 2012 blood.14 With these findings, there is increasing awareness for Revised: March 26, 2012 engineering amphiphilic materials, which, similar to living Published: April 19, 2012 © 2012 American Chemical Society 1233 dx.doi.org/10.1021/bm201791p | Biomacromolecules 2012, 13, 1233−1239 Biomacromolecules Communication adsorption.20 When compared to the controls [poly- was used as the minor component.32 A ratio of 15−20 mol % (dimethylsiloxane) and the base coat of SABCs: poly(styrene- was used, sufficient to provide covalent attachments to the b-ethylene butylene-b-styrene)], the surfaces composed of the substrate (glass/silica surface) as well as to improve the stability SABCs showed lower BSA adsorption. More recently, of the coatings through interchain cross-linking.33,34 amphiphilic self-assembled monolayers (SAMs), likewise composed of fluoroalkyl and PEG groups, were also reported − ■ RESULT AND DISCUSSION as potential nonfouling surfaces.26 28 The protein adsorption To prevent the carboxylate anion of the zwitterion from studies of these SAMs yielded similar results, where the 35,36 amphiphilic systems were more effective in resisting nonspecific retarding the ROMP kinetics, the monomers were protein adsorption than only PEG or fluoroalkyl SAMs. synthesized as cationic precursors through the quaternization These examples show that besides wettability, compositional of a norbornene-based tertiary amine (Scheme S1 and Figures − and morphological heterogeneities are also critical parameters S1 S6 in the Supporting Information). The resulting for designing effective nonfouling materials. Although there are quaternary ammonium precursor monomers were then several examples of amphiphilic materials obtained by copolymerized in a random fashion with 5-bicycloheptenyl incorporation of either hydrocarbon or fluorine-based hydro- triethoxysilane (Scheme S3 in the Supporting Information) via ROMP. The monomer compositions and the molecular weights phobic moieties, no direct comparison between both has been 1 reported.29,30 Moreover, all of these systems employ PEG as of the resulting copolymers were determined using H NMR the hydrophilic component, which is known to be unstable in end-group analysis and were in strong agreement with the the presence of oxygen and transition metals, reducing the theoretical values, indicating successful polymerization. De- lifetime of the material.31 Therefore, the quest to identify the tailed synthetic procedures as well as molecular weight most effective components that yield optimal amphiphilic characterization of the copolymers can be found in the − systems is still ongoing. Supporting Information (Figures S7 S12, Table S1). Surfaces fl In this Communication, we introduce a series of novel were prepared via spin coating a 1% w/v tri uoroethanol amphiphilic polybetaine copolymers composed of zwitterionic solution of each polymer on a freshly cleaned silica wafer. functionalities coupled with hydrophilic/hydrophobic alkyl side These surfaces were then dried under vacuum to remove the chains within the same repeat unit (Figure 1). This unique remaining solvent, subjected to hydrolysis, and cured above the condensation temperature of the ethoxysilane units. The resulting cationic coatings (Poly[NR(+)-co-NSi]) were then postfunctionalized using dilute base (0.1 M NaOH) to obtain their corresponding zwitterionic counterparts (Poly[NRZI-co- NSi]).32,35 Detailed surface characterization of the ring-opening transformation of Poly[NF(+)-co-NSi] can be found in the Supporting Information (Figure S13), while the data for -co- -co- Poly[NOEG(+) NSi] and Poly[NC8(+) NSi])were reported elsewhere.32 Coating thicknesses were measured using single-wave ellipsometry and were in the range of 20 to 35 nm. The performance of a coating is strongly dependent on its Figure 1. Summary of copolymers synthesized. Nomenclature: R = surface properties, such as wettability, morphology, and substituent, N = norbornene, ZI = zwitterion, Si = 5-bicycloheptenyl interfacial characteristics. Therefore, prior to protein adsorption triethoxysilane repeat unit, OEG = oligoethylene glycol, C8 = octyl, studies, detailed surface characterization was performed on the and F = 1H,1H,2H,2H-perfluorooctyl. coatings. The wettability of the zwitterionic coatings, Poly- [NRZI-co-NSi], was analyzed via contact angle (CA) measure- design allowed us to systematically tune the amphiphilicity of ments using the sessile drop technique. Advancing and receding the whole system at the repeat unit level. In this system, a CAs were measured with water and n-hexadecane. While water betaine was employed as the hydrophilic component, and the was used to determine the relative hydrophilicity/hydro- substituent (R) was varied as oligoethylene glycol (OEG), octyl phobicity of the coatings, n-hexadecane was employed to fl (C8), and uorinated (F) chains to systematically tune the determine their lipophilicity/lipophobicity. The results are overall amphiphilicity. All polymers were synthesized as silane- summarized in Table 1. (Surface characterization results of the containing copolymers via ring-opening metathesis polymer- cationic precursor coatings can be found in
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