Fundamental Principles of the Thermodynamics and Kinetics of Protein Adsorption to Material Surfaces.

Protein adsorption is important for essentially any process that involves the contact of a protein-containing solution and a material surface, with the resulting formation of the adsorbed layer of protein determined by the thermodynamics and kinetics of the system involved. This paper presents an overview of the fundamentals of these processes. First, the hierarchical structure of proteins and the types of bonding that stabilize a protein's native-state structure are presented.

In Vitro Thrombogenicity Testing of Biomaterials.

The short- and long-term thrombogenicity of implant materials is still unpredictable, which is a significant challenge for the treatment of cardiovascular diseases. A knowledge-based approach for implementing biofunctions in materials requires a detailed understanding of the medical device in the biological system. In particular, the interplay between material and blood components/cells as well as standardized and commonly acknowledged in vitro test methods allowing a reproducible categorization of the material thrombogenicity requires further attention.

The impacts of warming and hypoxia on the performance of an obligate ram ventilator.

Climate change is causing the warming and deoxygenation of coastal habitats like Chesapeake Bay that serve as important nursery habitats for many marine fish species. As conditions continue to change, it is important to understand how these changes impact individual species' behavioral and metabolic performance. The sandbar shark () is an obligate ram-ventilating apex predator whose juveniles use Chesapeake Bay as a nursery ground up to 10 years of age.

The blood compatibility challenge. Part 2: Protein adsorption phenomena governing blood reactivity.

The adsorption of proteins is the initiating event in the processes occurring when blood contacts a "foreign" surface in a medical device, leading inevitably to thrombus formation. Knowledge of protein adsorption in this context has accumulated over many years but remains fragmentary and incomplete. Moreover, the significance and relevance of the information for blood compatibility are not entirely agreed upon in the biomaterials research community.

BloodSurf 2017: News from the blood-biomaterial frontier.

From stents and large-diameter vascular grafts, to mechanical heart valves and blood pumps, blood-contacting devices are enjoying significant clinical success owing to the application of systemic antiplatelet and anticoagulation therapies. On the contrary, research into material and device hemocompatibility aimed at alleviating the need for systemic therapies has suffered a decline. This research area is undergoing a renaissance fueled by recent fundamental insights into coagulation and inflammation that are offering new avenues of investigation, the growing recognition of the limitations facing existing therapeutic approaches, and the severity of the cardiovascular disorders epidemic.

High-performance nanomaterials formed by rigid yet extensible cyclic β-peptide polymers.

Organisms have evolved biomaterials with an extraordinary convergence of high mechanical strength, toughness, and elasticity. In contrast, synthetic materials excel in stiffness or extensibility, and a combination of the two is necessary to exceed the performance of natural biomaterials. We bridge this materials property gap through the side-chain-to-side-chain polymerization of cyclic β-peptide rings.

Projecting shifts in thermal habitat for 686 species on the North American continental shelf.

Recent shifts in the geographic distribution of marine species have been linked to shifts in preferred thermal habitats. These shifts in distribution have already posed challenges for living marine resource management, and there is a strong need for projections of how species might be impacted by future changes in ocean temperatures during the 21st century. We modeled thermal habitat for 686 marine species in the Atlantic and Pacific oceans using long-term ecological survey data from the North American continental shelves.

Molecular modeling to predict peptide accessibility for peptide-functionalized hydrogels.

Peptide-functionalized (PF) hydrogels are being widely investigated by the tissue engineering and regenerative medicine communities for a broad range of applications because of their unique potential to mimic the natural extracellular matrix and promote tissue regeneration. In order for these complex material systems to perform their intended bioactive function (e.g.

Application of advanced sampling and analysis methods to predict the structure of adsorbed protein on a material surface.

The use of standard molecular dynamics simulation methods to predict the interactions of a protein with a material surface have the inherent limitations of lacking the ability to determine the most likely conformations and orientations of the adsorbed protein on the surface and to determine the level of convergence attained by the simulation. In addition, standard mixing rules are typically applied to combine the nonbonded force field parameters of the solution and solid phases the system to represent interfacial behavior without validation. As a means to circumvent these problems, the authors demonstrate the application of an efficient advanced sampling method (TIGER2A) for the simulation of the adsorption of hen egg-white lysozyme on a crystalline (110) high-density polyethylene surface plane.

Stirred, shaken, or stagnant: What goes on at the blood-biomaterial interface.

There is a widely recognized need to improve the performance of vascular implants and external medical devices that come into contact with blood by reducing adverse reactions they cause, such as thrombosis and inflammation. These reactions lead to major adverse cardiovascular events such as heart attacks and strokes. Currently, they are managed therapeutically.

Physiological stress and post-release mortality of white marlin (Kajikia albida) caught in the United States recreational fishery.

White marlin, a highly migratory pelagic marine fish, support important commercial and recreational fisheries throughout their range in the tropical and subtropical Atlantic Ocean. More than 10 000 individuals can be caught annually in the United States recreational fishery, of which the vast majority are captured on circle hooks and released alive. The probability of post-release mortality of white marlin released from circle hooks has been documented to be <0.

Cluster analysis of molecular simulation trajectories for systems where both conformation and orientation of the sampled states are important.

Clustering methods have been widely used to group together similar conformational states from molecular simulations of biomolecules in solution. For applications such as the interaction of a protein with a surface, the orientation of the protein relative to the surface is also an important clustering parameter because of its potential effect on adsorbed-state bioactivity. This study presents cluster analysis methods that are specifically designed for systems where both molecular orientation and conformation are important, and the methods are demonstrated using test cases of adsorbed proteins for validation.

Multiscale approach for the construction of equilibrated all-atom models of a poly(ethylene glycol)-based hydrogel.

A multiscale modeling approach is presented for the efficient construction of an equilibrated all-atom model of a cross-linked poly(ethylene glycol) (PEG)-based hydrogel using the all-atom polymer consistent force field (PCFF). The final equilibrated all-atom model was built with a systematic simulation toolset consisting of three consecutive parts: (1) building a global cross-linked PEG-chain network at experimentally determined cross-link density using an on-lattice Monte Carlo method based on the bond fluctuation model, (2) recovering the local molecular structure of the network by transitioning from the lattice model to an off-lattice coarse-grained (CG) model parameterized from PCFF, followed by equilibration using high performance molecular dynamics methods, and (3) recovering the atomistic structure of the network by reverse mapping from the equilibrated CG structure, hydrating the structure with explicitly represented water, followed by final equilibration using PCFF parameterization. The developed three-stage modeling approach has application to a wide range of other complex macromolecular hydrogel systems, including the integration of peptide, protein, and/or drug molecules as side-chains within the hydrogel network for the incorporation of bioactivity for tissue engineering, regenerative medicine, and drug delivery applications.

TIGER2 with solvent energy averaging (TIGER2A): An accelerated sampling method for large molecular systems with explicit representation of solvent.

The recently developed "temperature intervals with global exchange of replicas" (TIGER2) accelerated sampling method is found to have inaccuracies when applied to systems with explicit solvation. This inaccuracy is due to the energy fluctuations of the solvent, which cause the sampling method to be less sensitive to the energy fluctuations of the solute. In the present work, the problem of the TIGER2 method is addressed in detail and a modification to the sampling method is introduced to correct this problem.

Evaluation of the Effectiveness of Surfactants and Denaturants to Elute and Denature Adsorbed Protein on Different Surface Chemistries.

The elution and/or denaturation of proteins from material surfaces by chemical excipients such as surfactants and denaturants is important for numerous applications including medical implant reprocessing, bioanalyses, and biodefense. The objective of this study was to develop and apply methods to quantitatively assess how surface chemistry and adsorption conditions influence the effectiveness of three commonly used surfactants (sodium dodecyl sulfate, n-octyl-β-d-glucoside, and 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate) and two denaturants (guanidium hydrochloride and urea) to elute protein (hen egg white lysozyme and bovine pancreatic ribonuclease A) from three different surface chemistries (silica glass, poly(methyl methacrylate), and high-density polyethylene). The structure and bioactivity of residual protein on the surface following elution were characterized using circular dichroism spectropolarimetry and enzyme assays to assess the extent of protein denaturation.

Abiotic effects on effluent dissolved organic nitrogen along an estuarine transect.

Biological nutrient removal is a process commonly used in water resource recovery facilities to reduce dissolved inorganic nitrogen (DIN) concentrations in effluent; this process is less effective at removing all of the effluent dissolved organic nitrogen (EDON). The goal of this study was to investigate the fate of EDON after it undergoes the disinfection process and enters receiving waters. The authors quantified the abiotic effects of effluent exposure to sunlight, increased salinity, and a combination of the two factors.

Parameterization of an interfacial force field for accurate representation of peptide adsorption free energy on high-density polyethylene.

Interfacial force field (IFF) parameters for use with the CHARMM force field have been developed for interactions between peptides and high-density polyethylene (HDPE). Parameterization of the IFF was performed to achieve agreement between experimental and calculated adsorption free energies of small TGTG-X-GTGT host-guest peptides (T = threonine, G = glycine, and X = variable amino-acid residue) on HDPE, with ±0.5 kcal/mol agreement.

Experimental characterization of adsorbed protein orientation, conformation, and bioactivity.

Protein adsorption on material surfaces is a common phenomenon that is of critical importance in many biotechnological applications. The structure and function of adsorbed proteins are tightly interrelated and play a key role in the communication and interaction of the adsorbed proteins with the surrounding environment. Because the bioactive state of a protein on a surface is a function of the orientation, conformation, and accessibility of its bioactive site(s), the isolated determination of just one or two of these factors will typically not be sufficient to understand the structure-function relationships of the adsorbed layer.

Protease-degradable PEG-maleimide coating with on-demand release of IL-1Ra to improve tissue response to neural electrodes.

Neural electrodes are an important part of brain-machine interface devices that can restore functionality to patients with sensory and movement disorders. Chronically implanted neural electrodes induce an unfavorable tissue response which includes inflammation, scar formation, and neuronal cell death, eventually causing loss of electrode function. We developed a poly(ethylene glycol) hydrogel coating for neural electrodes with non-fouling characteristics, incorporated an anti-inflammatory agent, and engineered a stimulus-responsive degradable portion for on-demand release of the anti-inflammatory agent in response to inflammatory stimuli.

Adsorption-induced changes in ribonuclease A structure and enzymatic activity on solid surfaces.

Ribonuclease A (RNase A) is a small globular enzyme that lyses RNA. The remarkable solution stability of its structure and enzymatic activity has led to its investigation to develop a new class of drugs for cancer chemotherapeutics. However, the successful clinical application of RNase A has been reported to be limited by insufficient stability and loss of enzymatic activity when it was coupled with a biomaterial carrier for drug delivery.

Protein helical structure determination using CD spectroscopy for solutions with strong background absorbance from 190 to 230nm.

Conventional empirical methods for the quantification of the helical content of proteins in solution using circular dichroism (CD) primarily rely on spectral data acquired between wavelengths of 190 and 230nm. The presence of chemical species in a protein solution with strong absorbance within this range can interfere with the ability to use these methods for the determination of the protein's helical structure. The objective of this research was to overcome this problem by developing a method for CD spectral analysis that relies on spectral features above this wavelength range.

Perspectives on the simulation of protein-surface interactions using empirical force field methods.

Protein-surface interactions are of fundamental importance for a broad range of applications in the fields of biomaterials and biotechnology. Present experimental methods are limited in their ability to provide a comprehensive depiction of these interactions at the atomistic level. In contrast, empirical force field based simulation methods inherently provide the ability to predict and visualize protein-surface interactions with full atomistic detail.

The Langmuir isotherm: a commonly applied but misleading approach for the analysis of protein adsorption behavior.

The Langmuir adsorption isotherm provides one of the simplest and most direct methods to quantify an adsorption process. Because isotherm data from protein adsorption studies often appear to be fit well by the Langmuir isotherm model, estimates of protein binding affinity have often been made from its use despite that fact that none of the conditions required for a Langmuir adsorption process may be satisfied for this type of application. The physical events that cause protein adsorption isotherms to often provide a Langmuir-shaped isotherm can be explained as being due to changes in adsorption-induced spreading, reorientation, clustering, and aggregation of the protein on a surface as a function of solution concentration in contrast to being due to a dynamic equilibrium adsorption process, which is required for Langmuir adsorption.

Determination of orientation and adsorption-induced changes in the tertiary structure of proteins on material surfaces by chemical modification and peptide mapping.

The labeling of amino acid residues followed by peptide mapping via mass spectrometry (AAL/MS) is a promising technique to provide detailed information on the adsorption-induced changes in its solvent accessibility. However, the potential of this method for the study of adsorbed protein structure is largely undeveloped at this time. The objective of this research was therefore to extend these capabilities by developing and applying AAL/MS techniques for a range of amino acid types to identify the dominant configurations of an adsorbed protein on a material surface.