Nonfouling Property of Zwitterionic Cysteine Surface

Abstract

Applications of implantable bioelectronics for analytical and curative purposes are currently limited by their poor long-term biofunctionality in physiological media and nonspecific interactions with biomolecules. In an attempt to prolong in vivo functionality, recent advances in surface modifications have demonstrated that zwitterionic coatings can rival the performance of conventional poly(ethylene glycol) polymers in reducing nonspecific protein fouling. Herein, we report the fabrication of a very thin layer of nonfouling zwitterionic cysteine surface capable of protecting implantable bioelectronics from nonspecific adsorption of plasma proteins. This work is the first of its kind to fabricate, through solution chemistry, a cysteine surface exhibiting zwitterionic state as high as 88% and to demonstrate antibiofouling under the exposure of bovine serum albumin (BSA) and human serum. The fabricated surface utilized a minimal amount of gold substrate, approximately 10 nm, and an extremely thin antifouling layer at 1.14 nm verified by ellipsometry. X-ray photoelectron spectroscopy assessment of the nitrogen (N1s) and carbon (C1s) spectra conclude that 87.8% of the fabricated cysteine surface is zwitterionic, 2.5% is positively charged, and 9.6% is noncharged. Antibiofouling performance of the cysteine surface is quantitatively determined by bicinchoninic acid (BCA) protein assay as well as qualitatively confirmed using scanning electron spectroscopy. Cysteine surfaces demonstrated a BSA fouling of 3.9 ± 4.84% μg/cm(2), which is 93.6% and 98.5% lower than stainless steel and gold surfaces, respectively. Surface plasmon resonance imaging analysis returned similar results and suggest that a thinner cysteine coating will enhance performance. Scanning electron microscopy confirmed the results of BCA assay and suggested that the cysteine surface demonstrated a 69% reduction to serum fouling. The results reported in this paper demonstrate that it is possible to achieve a highly zwitterionic surface through solution chemistry on a macroscopic level that is capable of improving biocompatibility of long-term implantable bioelectronics.

Resistance of Zwitterionic Peptide Monolayers to Biofouling

“…Early examples of (pseudo)zwitterionic SAMs includes quaternary ammonium, sulfonate and phosphate residues 10 , and phosphorylcholine 11 , and several other works, using a variety of zwitterionic SAMs, have followed. [12][13][14][15] Considered as materials, peptides are polymers with the advantages of well-developed and highly controlled preparation methods, a range of natural and synthetic amino acids for tuning the properties of the peptides, biodegradability, and often high biocompatibility. [16][17][18] These advantages have been exploited for engineering of interfaces via surface attachment of peptides, for example in the preparation of model systems in surface science 19 , for functionalization of implants 20 , biosensor development 21 , to explore surface interaction mechanisms in bioadhesion 22 and also for general antifouling purposes.…”

Crosslinking behaviors and mechanical properties of curable PDMS and PEG films with various contents of glycidyl methacrylate

“…Note that the epoxy groups on the film surface can be readily functionalized with various bio‐materials having amphiphilic property, such as amino acids (cysteine, lysine, serine, etc.). For example, the cysteine can be readily functionalized on the surface via thiol‐epoxy click reaction and the zwitterionic property can be obtained on the film surface for anti‐fouling ability, which will be reported in the future.…”

Development of a SERS strategy to overcome the nanoparticle stabilisation effect in serum-containing samples: Application to the quantification of dopamine in the culture medium of PC-12 cells

“…These properties result from the hydration of the polymer and the balance of the charges, which negatively affect the thermodynamic parameters of the protein binding [43]. The L-cysteine amino-acid was therefore chosen as it forms a zwitterion at physiological pH, is commercially available at low cost and as some anti-fouling studies have already been conducted with this molecule [44]. Unfortunately, no aggregation could be observed when the PC-12 culture medium was added to AuNPs functionalised with L-cysteine.…”