Investigating the Sequence Specific Adsorption Behavior of Polypeptides at the Solid/Liquid Interface.

Polymer adsorption at the solid/liquid interface depends not only on the chemical composition of the polymer but also on the specific placement of the monomers along the polymer sequence. However, challenges in designing polymers with well-controlled sequences have limited explorations into the role of polymer sequence on adsorption behavior to molecular simulations. Here, we demonstrate how the sequence control offered by polypeptide synthesis can be utilized to study the effects small changes in polymer sequence have on polymer adsorption behavior at the solid/liquid interface. Through a combination of quartz crystal microbalance with dissipation monitoring and total internal reflection ellipsometry, we study the adsorption behavior of three polypeptides, consisting of 90% lysine and 10% cysteine, onto a gold surface. We find different mechanisms are responsible for the adsorption of polypeptides and the resulting conformation on the surface. The initial adsorption of the polypeptides is driven by electrostatic interactions between the polylysine and the gold surface. Once adsorbed, the cysteine undergoes a thiol-Au reaction with the surface, altering the conformation of the polymer layer. Our findings suggest the conformation of the polypeptide layer is dependent on the placement of the cysteines within the sequence; polypeptide chains with evenly spaced cysteine groups adopt a more tightly bound "train" conformation as compared to polypeptides with closely grouped cysteine groups. We envision that the methodologies presented here to study sequence specific adsorption behaviors using polypeptides could be a valuable tool to complement molecular simulations studies.

Nanoparticle dynamics in hydrogel networks with controlled defects.

The effect of nanoscale defects on nanoparticle dynamics in defective tetra-poly(ethylene glycol) (tetra-PEG) hydrogels is investigated using single particle tracking. In a swollen nearly homogeneous hydrogel, PEG-functionalized quantum dot (QD) probes with a similar hydrodynamic diameter (dh = 15.1 nm) to the mesh size (〈ξs〉 = 16.3 nm), are primarily immobile. As defects are introduced to the network by reaction-tuning, both the percentage of mobile QDs and the size of displacements increase as the number and size of the defects increase with hydrolysis time, although a large portion of the QDs remain immobile. To probe the effect of nanoparticle size on dynamics in defective networks, the transport of dh = 47.1 nm fluorescent polystyrene (PS) and dh = 9.6 nm PEG-functionalized QDs is investigated. The PS nanoparticles are immobile in all hydrogels, even in highly defective networks with an open structure. Conversely, the smaller QDs are more sensitive to perturbations in the network structure with an increased percentage of mobile particles and larger diffusion coefficients compared to the larger QDs and PS nanoparticles. The differences in nanoparticle mobility as a function of size suggests that particles of different sizes probe different length scales of the defects, indicating that metrics such as the confinement ratio alone cannot predict bulk dynamics in these systems. This study provides insight into designing hydrogels with controlled transport properties, with particular importance for degradable hydrogels for drug delivery applications.

pH-Mediated nanoparticle dynamics in hydrogel nanocomposites.

The effect of static silica particles on the dynamics of quantum dot (QD) nanoparticles grafted with a poly(ethylene glycol) (PEG) brush in hydrogel nanocomposites is investigated using single particle tracking (SPT). At a low volume fraction of homogeneously dispersed silica (Φ = 0.005), two distinct populations of PEG-QDs are observed, localized and mobile, whereas almost all PEG-QDs are mobile in neat hydrogel (Φ = 0.0). Increasing the silica particle concentration (Φ = 0.01, 0.1) results in an apparent change in the network structure, confounding the impact of silica on PEG-QD dynamics. The localized behavior of PEG-QDs is attributed to pH-mediated attraction between the PEG brush on the probe and surface silanol groups of silica. Using quartz crystal microbalance with dissipation (QCM-D), the extent of this interaction is investigated as a function of pH. At pH 5.8, the PEG brush on the probe can hydrogen bond with the silanol groups on silica, leading to adsorption of PEG-QDs. In contrast, at pH 9.2, silanol groups are deprotonated and PEG-QD is unable to hydrogen bond with silica leading to negligible adsorption. To test the effect of pH, PEG-QD dynamics are further investigated in hydrogel nanocomposites at Φ = 0.005. SPT agrees with the QCM-D results; at pH 5.8, PEG-QDs are localized whereas at pH 9.2 the PEG-QDs are mobile. This study provides insight into controlling probe transport through hydrogel nanocomposites using pH-mediated interactions, with implications for tuning transport of nanoparticles underlying drug delivery and nanofiltration.

Nanoparticle diffusion during gelation of tetra poly(ethylene glycol) provides insight into nanoscale structural evolution.

Single particle tracking (SPT) of PEG grafted nanoparticles (NPs) was used to examine the gelation of tetra poly(ethylene glycol) (TPEG) succinimidyl glutarate (TPEG-SG) and amine (TPEG-A) terminated 4-armed stars. As concentration was decreased from 40 to 20 mg mL-1, the onset of network formation, tgel, determined from rheometry increased from less than 2 to 44 minutes. NP mobility increased as polymer concentration decreased in the sol state, but remained diffusive at times past the tgel determined from rheometry. Once in the gel state, NP mobility decreased, became sub-diffusive, and eventually localized in all concentrations. The NP displacement distributions were investigated to gain insight into the nanoscale environment. In these relatively homogeneous gels, the onset of sub-diffusivity was marked by a rapid increase in dynamic heterogeneity followed by a decrease consistent with a homogeneous network. We propose a gelation mechanism in which clusters initially form a heterogeneous structure which fills in to form a fully gelled relatively homogenous network. This work aims to examine the kinetics of TPEG gelation and the homogeneity of these novel gels on the nanometer scale, which will aid in the implementation of these gels in biomedical or filtration applications.