Probing Resistance to Protein Adsorption of Oligo(ethylene glycol)-Terminated Self-Assembled Monolayers by Scanning Force Microscopy

Abstract

Functionalized scanning force microscope (SFM) probes were used to investigate and to mimic the interaction between fibrinogen and self-assembled monolayers (SAMs) of methoxytri(ethylene glycol) undecanethiolates −S(CH2)11(OCH2CH2)3OCH3 (EG3-OMe) on gold and silver surfaces. The SAMs on gold are resistant to protein adsorption, whereas the films on silver adsorb variable amounts of fibrinogen. Experiments were performed with both charged and hydrophobic tips as models for local protein structures to determine the influence of these parameters on the interaction with the SAMs. A striking difference between the two monolayers was established when the forces were measured in an aqueous environment with hydrophobic probes. While a long-range attractive hydrophobic interaction was observed for the EG3-OMe on silver, a repulsive force was measured for EG3-OMe on gold. The strong dependence of the repulsive force for the EG3-OMe-gold system upon the solution ionic strength suggests that this interaction has a significant electrostatic contribution. The observed differences are attributed to the distinct molecular conformations of the oligo(ethylene glycol) tails on the gold-supported (helical) and silver-supported (“all-trans”) monolayers. A comparison of the force/distance curves for the EG3-OMe SAMs with those measured under identical conditions on end-grafted poly(ethylene glycol) (PEG 2000) on gold further emphasizes that the nature of the repulsive forces originating from the short-chain oligomers is unique and not related to a “steric repulsion” effect.

Synthesis and Single Molecule Force Spectroscopy of Graft Copolymers of Poly(2-hydroxyethyl methacrylate-g-ethylene glycol)

“…Prior work reported in the literature related to the approach data presented in this study include nanomechanical experiments on thiol end-grafted PEG2K brushes on Au using a hydrophobically modified C16 probe tip which show a purely repulsive interaction on approach for D < 12 nm. 56 In our experiments, in addition to the EDL repulsion imparted by the 86-90% surface area taken up by the Au substrate, the 10%-14% of the surface area covered by the graft copolymer mushrooms may contribute configurational entropy, enthalpic deformability due to noncovalent intramolecular interactions and/or polymer-solvent interactions, and hydration repulsion as well as attractive van der Waals and hydrophobic interactions depending on the polymer surface conformation. In PBS the poly(HEMA-g-EG) 16K shows a net attractive force for D < ∼10 nm (R g (DMF) ) 18.5 nm with R g (PEG2K side chains) ) 3.6 nm), 56 thus suggesting that the polymer is contributing enough van der Waals and/or hydrophobic interactions from exposed functional groups to outweigh the EDL repulsion imparted by the Au or the PEG2K.…”

Protein Adsorption on Supported Phospholipid Bilayers

“…It is, however, clear through recent systematic experimental work and earlier experimental documentation that certain hydrophilic surfaces are quite protein resistant (5,(9)(10)(11)(40)(41)(42). Consequently, the bonding and structure of water at the surfaces, with which proteins interact, are important.…”

“…Lipid films at interfaces have actually previously been shown to be quite efficient in preventing protein adsorption (4-7), and have also been shown to limit cell attachment (8) (a fact that can probably be directly related to the low affinity to protein adsorption on the membrane; if proteins do not bind, cells will not find attachment sites). The actual mechanisms behind the protein resistance are, however, still poorly understood, although recent important experimental data have addressed, e.g., the role of the polarity of functional groups (9) interacting with proteins, surface wettability (10), and the role of the hydration layer of the protein-resistant surfaces (11). Recently the influence of surface polarizability and surface hydration layer thickness on the protein adsorption energetics was treated theoretically (12).…”

Direct Measurement of Glycosaminoglycan Intermolecular Interactions via High-Resolution Force Spectroscopy

“…The measurement of repulsive DLVO forces between nonpolymeric charged surfaces is well documented in the literature using both the surface force apparatus (and similar instruments) [46][47][48][49][50][51] and the atomic force microscope. [20][21][22][23]30,[52][53][54][55][56][57][58][59][60][61][62] All of the theoretical models presented in this paper employ constant surface charge boundary conditions, rather than constant potential, for two reasons. First, both the substrate and the tip were electrically isolated from each other and from the instrument ground and, therefore, not electrically connected to any source that would maintain them at a constant potential.…”