Recombinant Lignin Peroxidase with Superior Thermal Stability and Melanin Decolorization Efficiency in a Typical Human Skin-Mimicking Environment.

Recently, the desire for a safe and effective method for skin whitening has been growing in the cosmetics industry. Commonly used tyrosinase-inhibiting chemical reagents exhibit side effects. Thus, recent studies have focused on performing melanin decolorization with enzymes as an alternative due to the low toxicity of enzymes and their ability to decolorize melanin selectively. Herein, 10 different isozymes were expressed as recombinant lignin peroxidases (LiPs) from Phanerochaete chrysosporium (PcLiPs), and PcLiP isozyme 4 (PcLiP04) was selected due to its high stability and activity at pH 5.5 and 37 °C, which is close to human skin conditions. In vitro melanin decolorization results indicated that PcLiP04 exhibited at least 2.9-fold higher efficiency than that of well-known lignin peroxidase (PcLiP01) in a typical human skin-mimicking environment. The interaction force between melanin films measured by a surface forces apparatus (SFA) revealed that the decolorization of melanin by PcLiP04 harbors a disrupted structure, possibly interrupting π-π stacking and/or hydrogen bonds. In addition, a 3D reconstructed human pigmented epidermis skin model showed a decrease in melanin area to 59.8% using PcLiP04, which suggests that PcLiP04 exhibits a strong potential for skin whitening.

Real-time visualisation of ion exchange in molecularly confined spaces where electric double layers overlap.

Ion interactions with interfaces and transport in confined spaces, where electric double layers overlap, are essential in many areas, ranging from crevice corrosion to understanding and creating nano-fluidic devices at the sub 10 nm scale. Tracking the spatial and temporal evolution of ion exchange, as well as local surface potentials, in such extreme confinement situations is both experimentally and theoretically challenging. Here, we track in real-time the transport processes of ionic species (LiClO4) confined between a negatively charged mica surface and an electrochemically modulated gold surface using a high-speed in situ sensing Surface Forces Apparatus. With millisecond temporal and sub-micrometer spatial resolution we capture the force and distance equilibration of ions in the confinement of D ≈ 2-3 nm in an overlapping electric double layer (EDL) during ion exchange. Our data indicate that an equilibrated ion concentration front progresses with a velocity of 100-200 µm s-1 into a confined nano-slit. This is in the same order of magnitude and in agreement with continuum estimates from diffusive mass transport calculations. We also compare the ion structuring using high resolution imaging, molecular dynamics simulations, and calculations based on a continuum model for the EDL. With this data we can predict the amount of ion exchange, as well as the force between the two surfaces due to overlapping EDLs, and critically discuss experimental and theoretical limitations and possibilities.

Prussian Blue Nanolayer-Embedded Separator for Selective Segregation of Nickel Dissolution in High Nickel Cathodes.

Transition metal layered oxides (LiNixCoyMn1-x-yO2, NCM) have been considered as one of the most promising cathodes for lithium-ion batteries used in long-mileage electric vehicles and energy storage systems. Despite its potential interest, dissolved transition metal (TM) ions toward anode sides can catalyze parasitic reactions such as electrolytic decomposition and dendritic Li growth, ultimately leading to catastrophic safety hazards. In this study, we demonstrate that Prussian Blue (PB) nanoparticles anchored to a commercial PE separator significantly reduce cell resistance and effectively suppress TM crossover during cycling, even under harsh conditions that accelerate Ni dissolution. Therefore, using a PB-coated separator in a harsh condition to intentionally dissolve Ni2+ ions at a high cutoff potential of 4.6 V, NCM||graphite full cells maintain 50.8% of their initial capacity at the 150th cycle. Scalable production of PB-coated separator through the facile synthetic methods can help establish a new research direction for the design of high-energy-density batteries.

Peptidomimetic Wet-Adhesive PEGtides with Synergistic and Multimodal Hydrogen Bonding.

The remarkable underwater adhesion of mussel foot proteins has long been an inspiration in the design of peptidomimetic materials. Although the synergistic wet adhesion of catechol and lysine has been recently highlighted, the critical role of the polymeric backbone has remained largely underexplored. Here, we present a peptidomimetic approach using poly(ethylene glycol) (PEG) as a platform to evaluate the synergistic compositional relation between the key amino acid residues (i.e., DOPA and lysine), as well as the role of the polyether backbone in interfacial adhesive interactions. A series of PEG-based peptides (PEGtides) were synthesized using functional epoxide monomers corresponding to catechol and lysine via anionic ring-opening polymerization. Using a surface force apparatus, highly synergistic surface interactions among these PEGtides with respect to the relative compositional ratio were revealed. Furthermore, the critical role of the catechol-amine synergy and diverse hydrogen bonding within the PEGtides in the superior adhesive interactions was verified by molecular dynamics simulations. Our study sheds light on the design of peptidomimetic polymers with reduced complexity within the framework of a polyether backbone.

Mussel-Inspired Multiloop Polyethers for Antifouling Surfaces.

Despite the widespread use of polymers for antifouling coatings, the effect of the polymeric topology on the antifouling property has been largely underexplored. Unlike conventional brush polymers, a loop conformation often leads to strong steric stabilization of surfaces and antifouling and lubricating behavior owing to the large excluded volume and reduced chain ends. Herein, we present highly antifouling multiloop polyethers functionalized with a mussel-inspired catechol moiety with varying loop dimensions. Specifically, a series of polyethers with varying catechol contents were synthesized via anionic ring-opening polymerization by using triethylene glycol glycidyl ether (TEG) and catechol-acetonide glycidyl ether (CAG) to afford poly(TEG-co-CAG)n. The versatile adsorption and antifouling effects of multiloop polyethers were evaluated using atomic force microscopy and a quartz crystal microbalance with dissipation. Furthermore, the crucial role of the loop dimension in the antifouling properties was analyzed via a surface force apparatus and a cell attachment assay. This study provides a new platform for the development of versatile antifouling polymers with varying topologies.

Rates of cavity filling by liquids.

Understanding the fundamental wetting behavior of liquids on surfaces with pores or cavities provides insights into the wetting phenomena associated with rough or patterned surfaces, such as skin and fabrics, as well as the development of everyday products such as ointments and paints, and industrial applications such as enhanced oil recovery and pitting during chemical mechanical polishing. We have studied, both experimentally and theoretically, the dynamics of the transitions from the unfilled/partially filled (Cassie-Baxter) wetting state to the fully filled (Wenzel) wetting state on intrinsically hydrophilic surfaces (intrinsic water contact angle <90°, where the Wenzel state is always the thermodynamically favorable state, while a temporary metastable Cassie-Baxter state can also exist) to determine the variables that control the rates of such transitions. We prepared silicon wafers with cylindrical cavities of different geometries and immersed them in bulk water. With bright-field and confocal fluorescence microscopy, we observed the details of, and the rates associated with, water penetration into the cavities from the bulk. We find that unconnected, reentrant cavities (i.e., cavities that open up below the surface) have the slowest cavity-filling rates, while connected or non-reentrant cavities undergo very rapid transitions. Using these unconnected, reentrant cavities, we identified the variables that affect cavity-filling rates: (i) the intrinsic contact angle, (ii) the concentration of dissolved air in the bulk water phase (i.e., aeration), (iii) the liquid volatility that determines the rate of capillary condensation inside the cavities, and (iv) the presence of surfactants.

Development of Poly(methyl methacrylate)-Based Copolymers with Improved Heat Resistance and Reduced Moisture Absorption.

Poly(methyl methacrylate) (PMMA) is widely used as a transparent material for optical applications, owing to its high light transmittance. However, it exhibits poor heat resistance and high moisture absorption, leading to distortion and deformation upon exposure to elevated temperatures and/or moisture. These structural changes decrease the transparency of PMMA, critically limiting its applicability. In this study, we synthesized poly(methyl methacrylate-co-styrene-co-acrylamide) (PMSAm) as a reference polymer and introduced one of four different comonomers [N-phenylmaleimide (PMI), N-cyclohexylmaleimide (CHMI), allyltrimethylsilane (ATMS), or 2,2,2-trifluoroethyl methacrylate (TF)] as a means to improve heat resistance and reduce moisture absorption. Four series of PMMA-based random copolymers (PMSAm-PMI, PMSAm-CHMI, PMSAm-ATMS, and PMSAm-TF) were synthesized by conventional thermal radical polymerization. All of the polymers synthesized exhibited improved heat resistance, with PMSAm-CHMI exhibiting the highest glass transition temperature (Tg = 122.54 °C) and 5% weight loss thermal decomposition temperature (T5d = 343.40 °C) as well as the lowest thermal expansion coefficient (90.3 µm m-1 °C-1). The highest hydrophobicity was exhibited by PMSAm-TF, with a water contact angle of 78.9°, indicating higher hydrophobicity compared to that of pure PMMA (69.4°). More importantly, high transparency (∼90%) was exhibited by all of the synthesized polymers. Thus, our copolymerization strategy successfully addresses the limitations, i.e., low heat resistance and high moisture absorption, of conventional PMMA-based materials.

Multimodal Miniature Surface Forces Apparatus (µSFA) for Interfacial Science Measurements.

Advances in the research of intermolecular and surface interactions result from the development of new and improved measurement techniques and combinations of existing techniques. Here, we present a new miniature version of the surface forces apparatus-the µSFA-that has been designed for ease of use and multimodal capabilities with the retention of the capabilities of other SFA models including accurate measurements of the surface separation distance and physical characterization of dynamic and static physical forces (i.e., normal, shear, and friction) and interactions (e.g., van der Waals, electrostatic, hydrophobic, steric, and biospecific). The small physical size of the µSFA, compared to previous SFA models, makes it portable and suitable for integration into commercially available optical and fluorescence light microscopes, as demonstrated here. The large optical path entry and exit ports make it ideal for concurrent force measurements and spectroscopy studies. Examples of the use of the µSFA in combination with surface plasmon resonance (SPR) and Raman spectroscopy measurements are presented. Because of the short working distance constraints associated with Raman spectroscopy, an interferometric technique was developed and applied to calculate the intersurface separation distance based on Newton's rings. The introduction of the µSFA will mark a transition in SFA usage from primarily physical characterization to concurrent physical characterization with in situ chemical and biological characterization to study interfacial phenomena, including (but not limited to) molecular adsorption, fluid flow dynamics, the determination of surface species and morphology, and (bio)molecular binding kinetics.

Correlating steric hydration forces with water dynamics through surface force and diffusion NMR measurements in a lipid-DMSO-H2O system.

Dimethyl sulfoxide (DMSO) is a common solvent and biological additive possessing well-known utility in cellular cryoprotection and lipid membrane permeabilization, but the governing mechanisms at membrane interfaces remain poorly understood. Many studies have focused on DMSO-lipid interactions and the subsequent effects on membrane-phase behavior, but explanations often rely on qualitative notions of DMSO-induced dehydration of lipid head groups. In this work, surface forces measurements between gel-phase dipalmitoylphosphatidylcholine membranes in DMSO-water mixtures quantify the hydration- and solvation-length scales with angstrom resolution as a function of DMSO concentration from 0 mol% to 20 mol%. DMSO causes a drastic decrease in the range of the steric hydration repulsion, leading to an increase in adhesion at a much-reduced intermembrane distance. Pulsed field gradient NMR of the phosphatidylcholine (PC) head group analogs, dimethyl phosphate and tetramethylammonium ions, shows that the ion hydrodynamic radius decreases with increasing DMSO concentration up to 10 mol% DMSO. The complementary measurements indicate that, at concentrations below 10 mol%, the primary effect of DMSO is to decrease the solvated volume of the PC head group and that, from 10 mol% to 20 mol%, DMSO acts to gradually collapse head groups down onto the surface and suppress their thermal motion. This work shows a connection between surface forces, head group conformation and dynamics, and surface water diffusion, with important implications for soft matter and colloidal systems.

Underwater contact adhesion and microarchitecture in polyelectrolyte complexes actuated by solvent exchange.

Polyelectrolyte complexation is critical to the formation and properties of many biological and polymeric materials, and is typically initiated by aqueous mixing followed by fluid-fluid phase separation, such as coacervation. Yet little to nothing is known about how coacervates evolve into intricate solid microarchitectures. Inspired by the chemical features of the cement proteins of the sandcastle worm, here we report a versatile and strong wet-contact microporous adhesive resulting from polyelectrolyte complexation triggered by solvent exchange. After premixing a catechol-functionalized weak polyanion with a polycation in dimethyl sulphoxide (DMSO), the solution was applied underwater to various substrates whereupon electrostatic complexation, phase inversion, and rapid setting were simultaneously actuated by water-DMSO solvent exchange. Spatial and temporal coordination of complexation, inversion and setting fostered rapid (∼25 s) and robust underwater contact adhesion (Wad ≥ 2 J m(-2)) of complexed catecholic polyelectrolytes to all tested surfaces including plastics, glasses, metals and biological materials.

Contact Angle and Adhesion Dynamics and Hysteresis on Molecularly Smooth Chemically Homogeneous Surfaces.

Measuring truly equilibrium adhesion energies or contact angles to obtain the thermodynamic values is experimentally difficult because it requires loading/unloading or advancing/receding boundaries to be measured at rates that can be slower than 1 nm/s. We have measured advancing-receding contact angles and loading-unloading adhesion energies for various systems and geometries involving molecularly smooth and chemically homogeneous surfaces moving at different but steady velocities in both directions, ±V, focusing on the thermodynamic limit of ±V → 0. We have used the Bell Theory (1978) to derive expressions for the dynamic (velocity-dependent) adhesion energies and contact angles suitable for both (i) dynamic adhesion measurements using the classic Johnson-Kendall-Roberts (JKR, 1971) theory of "contact mechanics" and (ii) dynamic contact angle hysteresis measurements of both rolling droplets and syringe-controlled (sessile) droplets on various surfaces. We present our results for systems that exhibited both steady and varying velocities from V ≈ 10 mm/s to 1 nm/s, where in all cases but one, the advancing (V > 0) and receding (V < 0) adhesion energies and/or contact angles converged toward the same theoretical (thermodynamic) values as V → 0. Our equations for the dynamic contact angles are similar to the classic equations of Blake & Haynes (1969) and fitted the experimental adhesion data equally well over the range of velocities studied, although with somewhat different fitting parameters for the characteristic molecular length/dimension or area and characteristic bond formation/rupture lifetime or velocity. Our theoretical and experimental methods and results unify previous kinetic theories of adhesion and contact angle hysteresis and offer new experimental methods for testing kinetic models in the thermodynamic, quasi-static, limit. Our analyses are limited to kinetic effects only, and we conclude that hydrodynamic, i.e., viscous, and inertial effects do not play a role at the interfacial velocities of our experiments, i.e., V < (1-10) mm/s (for water and hexadecane, but for viscous polymers it may be different), consistent with previously reported studies.

Lipid domains control myelin basic protein adsorption and membrane interactions between model myelin lipid bilayers.

The surface forces apparatus and atomic force microscope were used to study the effects of lipid composition and concentrations of myelin basic protein (MBP) on the structure of model lipid bilayers, as well as the interaction forces and adhesion between them. The lipid bilayers had a lipid composition characteristic of the cytoplasmic leaflets of myelin from "normal" (healthy) and "disease-like" [experimental allergic encephalomyelitis (EAE)] animals. They showed significant differences in the adsorption mechanism of MBP. MBP adsorbs on normal bilayers to form a compact film (3-4 nm) with strong intermembrane adhesion (∼0.36 mJ/m(2)), in contrast to its formation of thicker (7-8 nm) swelled films with weaker intermembrane adhesion (∼0.13 mJ/m(2)) on EAE bilayers. MBP preferentially adsorbs to liquid-disordered submicron domains within the lipid membranes, attributed to hydrophobic attractions. These results show a direct connection between the lipid composition of membranes and membrane-protein adsorption mechanisms that affects intermembrane spacing and adhesion and has direct implications for demyelinating diseases.

Interaction Forces between Supported Lipid Bilayers in the Presence of PEGylated Polymers.

Using the surface forces apparatus (SFA), interaction forces between supported lipid bilayers were measured in the presence of polyethylene glycol and two other commercially available pegylated triblock polymers, Pluronic F68 and F127. Pluronic F68 has a smaller central hydrophobic block compared to F127 and therefore is more hydrophilic. The study aimed to unravel the effects of polymer architecture and composition on the interactions between the bilayers. Our keys findings show that below the critical aggregation concentration (CAC) of the polymers, a soft, weakly anchored, polymer layer is formed on the surface of the bilayers. The anchoring strength of this physisorbed layer was found to increase significantly with the size of the hydrophobic block of the polymer, and was strongest for the more hydrophobic polymer, F127. Above the CAC, a dense polymer layer, exhibiting gel-like properties, was found to rapidly grow on the bilayers even after mechanical disruption. The cohesive interaction maintaining the gel layer structure was found to be stronger for F127, and was also found to promote the formation of highly structured aggregates on the bilayers.

Stick-slip friction and wear of articular joints.

Stick-slip friction was observed in articular cartilage under certain loading and sliding conditions and systematically studied. Using the Surface Forces Apparatus, we show that stick-slip friction can induce permanent morphological changes (a change in the roughness indicative of wear/damage) in cartilage surfaces, even under mild loading and sliding conditions. The different load and speed regimes can be represented by friction maps--separating regimes of smooth and stick-slip sliding; damage generally occurs within the stick-slip regimes. Prolonged exposure of cartilage surfaces to stick-slip sliding resulted in a significant increase of surface roughness, indicative of severe morphological changes of the cartilage superficial zone. To further investigate the factors that are conducive to stick-slip and wear, we selectively digested essential components of cartilage: type II collagen, hyaluronic acid (HA), and glycosaminoglycans (GAGs). Compared with the normal cartilage, HA and GAG digestions modified the stick-slip behavior and increased surface roughness (wear) during sliding, whereas collagen digestion decreased the surface roughness. Importantly, friction forces increased up to 2, 10, and 5 times after HA, GAGs, and collagen digestion, respectively. Also, each digestion altered the friction map in different ways. Our results show that (i) wear is not directly related to the friction coefficient but (ii) more directly related to stick-slip sliding, even when present at small amplitudes, and that (iii) the different molecular components of joints work synergistically to prevent wear. Our results also suggest potential noninvasive diagnostic tools for sensing stick-slip in joints.

Surface-initiated self-healing of polymers in aqueous media.

Polymeric materials that intrinsically heal at damage sites under wet or moist conditions are urgently needed for biomedical and environmental applications. Although hydrogels with self-mending properties have been engineered by means of mussel-inspired metal-chelating catechol-functionalized polymer networks, biological self-healing in wet conditions, as occurs in self-assembled holdfast proteins in mussels and other marine organisms, is generally thought to involve more than reversible metal chelates. Here we demonstrate self-mending in metal-free water of synthetic polyacrylate and polymethacrylate materials that are surface-functionalized with mussel-inspired catechols. Wet self-mending of scission in these polymers is initiated and accelerated by hydrogen bonding between interfacial catechol moieties, and consolidated by the recruitment of other non-covalent interactions contributed by subsurface moieties. The repaired and pristine samples show similar mechanical properties, suggesting that the triggering of complete self-healing is enabled underwater by the formation of extensive catechol-mediated interfacial hydrogen bonds.

Adsorption mechanism of myelin basic protein on model substrates and its bridging interaction between the two surfaces.

Myelin basic protein (MBP) is an intrinsically disordered (unstructured) protein known to play an important role in the stability of myelin's multilamellar membrane structure in the central nervous system. The adsorption of MBP and its capacity to interact with and bridge solid substrates has been studied using a surface forces apparatus (SFA) and a quartz crystal microbalance with dissipation (QCM-D). Adsorption experiments show that MBP molecules adsorb to the surfaces in a swollen state before undergoing a conformational change into a more compact structure with a thickness of ∼3 nm. Moreover, this compact structure is able to interact with nearby mica surfaces to form adhesive bridges. The measured adhesion force (energy) between two bridged surfaces is 1.0 ± 0.1 mN/m, (Ead = 0.21 ± 0.02 mJ/m(2)), which is slightly smaller than our previously reported adhesion force of 1.7 mN/m (Ead = 0.36 mJ/m(2)) for MBP adsorbed on two supported lipid bilayers (Lee et al., Proc. Natl. Acad. Sci. U.S.A. 2014, 111, E768-E775). The saturated surface concentration of compact MBP on a single SiO2 surface reaches a stable value of 310 ± 10 ng/cm(2) regardless of the bulk MBP concentration. A kinetic three-step adsorption model was developed that accurately fits the adsorption data. The developed model is a general model, not limited to intrinsically disordered proteins, that can be extended to the adsorption of various chemical compounds that undergo chemical reactions and/or conformational changes upon adsorbing to surfaces. Taken together with our previously published data (Lee et al., Proc. Natl. Acad. Sci. U.S.A. 2014, 111, E768-E775), the present results confirm that conformational changes of MBP upon adsorption are a key for strong adhesion, and that such conformational changes are strongly dependent on the nature of the surfaces.

Developing a general interaction potential for hydrophobic and hydrophilic interactions.

We review direct force measurements on a broad class of hydrophobic and hydrophilic surfaces. These measurements have enabled the development of a general interaction potential per unit area, W(D) = -2γ(i)Hy exp(-D/D(H)) in terms of a nondimensional Hydra parameter, Hy, that applies to both hydrophobic and hydrophilic interactions between extended surfaces. This potential allows one to quantitatively account for additional attractions and repulsions not included in the well-known combination of electrostatic double layer and van der Waals theories, the so-called Derjaguin-Landau-Verwey-Overbeek (DLVO) theory. The interaction energy is exponentially decaying with decay length D(H) ≈ 0.3-2 nm for both hydrophobic and hydrophilic interactions, with the exact value of D(H) depending on the precise system and conditions. The pre-exponential factor depends on the interfacial tension, γ(i), of the interacting surfaces and Hy. For Hy > 0, the interaction potential describes interactions between partially hydrophobic surfaces, with the maximum hydrophobic interaction (i.e., two fully hydrophobic surfaces) corresponding to Hy = 1. Hydrophobic interactions between hydrophobic monolayer surfaces measured with the surface forces apparatus (SFA) are shown to be well described by the proposed interaction potential. The potential becomes repulsive for Hy < 0, corresponding to partially hydrophilic (hydrated) interfaces. Hydrated surfaces such as mica, silica, and lipid bilayers are discussed and reviewed in the context of the values of Hy appropriate for each system.

Bioinspired bottle-brush polymer exhibits low friction and Amontons-like behavior.

We report the design of a bottle-brush polymer whose architecture closely mimics the lubricating protein lubricin. Interaction forces, assessed using a Surface Forces Apparatus (SFA), between two mica surfaces fully covered by the polymer demonstrate that the polymer adopts a loop conformation giving rise to a weak and long-range repulsive interaction force between the surfaces. Under high compression, stronger repulsive forces appear due to the strong compression of the grafted pendant chains of the polymer. When submitted to shear, the system shows extremely low frictional forces dependent on the salinity of the medium. Friction coefficients measured for this system were as low as ~10(-3). Interestingly, the confined lubricating fluid obeys all three Amontons' laws. We explain this peculiar observation by the strong shear thinning of the confined fluid and the osmotic repulsive forces that dominate the overall (dynamic and equilibrium) surface interactions.

Relating domain size distribution to line tension and molecular dipole density in model cytoplasmic myelin lipid monolayers.

We fit the size distribution of liquid-ordered (L(o)) domains measured from fluorescence images of model cytoplasmic myelin monolayers with an equilibrium thermodynamic expression that includes the competing effects of line tension, λ, dipole density difference, Δm, and the mixing entropy. From these fits, we extract the line tension, λ, and dipole density difference, Δm, between the L(o) and liquid-disordered (L(d)) phases. Both λ and Δm decrease with increasing surface pressure, , although λ/Δm(2) remains roughly constant as the monolayer approaches the miscibility surface pressure. As a result, the mean domain size changed little with surface pressure, although the polydispersity increased significantly. The most probable domain radius was significantly smaller than that predicted by the energy alone, showing that the mixing entropy promotes a greater number of smaller domains. Our results also explain why domain shapes are stable; at equilibrium, only a small fraction of the domains are large enough to undergo theoretically predicted shape fluctuations. Monolayers based on the composition of myelin from animals with experimental allergic encephalomyelitis had slightly lower values of λ and Δm, and a higher area fraction of domains, than control monolayers at all . While it is premature to generalize these results to myelin bilayers, our results show that the domain distribution in myelin may be an equilibrium effect and that subtle changes in surface pressure and composition can alter the distribution of material in the monolayer, which will likely also alter the interactions between monolayers important to the adhesion of the myelin sheath.

Adaptive mechanically controlled lubrication mechanism found in articular joints.

Articular cartilage is a highly efficacious water-based tribological system that is optimized to provide low friction and wear protection at both low and high loads (pressures) and sliding velocities that must last over a lifetime. Although many different lubrication mechanisms have been proposed, it is becoming increasingly apparent that the tribological performance of cartilage cannot be attributed to a single mechanism acting alone but on the synergistic action of multiple "modes" of lubrication that are adapted to provide optimum lubrication as the normal loads, shear stresses, and rates change. Hyaluronic acid (HA) is abundant in cartilage and synovial fluid and widely thought to play a principal role in joint lubrication although this role remains unclear. HA is also known to complex readily with the glycoprotein lubricin (LUB) to form a cross-linked network that has also been shown to be critical to the wear prevention mechanism of joints. Friction experiments on porcine cartilage using the surface forces apparatus, and enzymatic digestion, reveal an "adaptive" role for an HA-LUB complex whereby, under compression, nominally free HA diffusing out of the cartilage becomes mechanically, i.e., physically, trapped at the interface by the increasingly constricted collagen pore network. The mechanically trapped HA-LUB complex now acts as an effective (chemically bound) "boundary lubricant"--reducing the friction force slightly but, more importantly, eliminating wear damage to the rubbing/shearing surfaces. This paper focuses on the contribution of HA in cartilage lubrication; however, the system as a whole requires both HA and LUB to function optimally under all conditions.