Phosphatidylcholine liposomes fill a special niche in alleviating osteoarthritis via intra-articular (IA) administration, attributed to their superlubricity at the articular cartilage surface, but their co-utilization as drug delivery vesicles in such therapy remains challenging as they may rupture under mechanical stress. Here, we describe cytoskeleton-inspired, supramolecular, self-assembled nanolipogels (NLGs), encompassing liposome-encased nanogels with a dynamic network formed by hydrogen bonding and cation-pi interactions, as a platform for simultaneous robust drug-delivery and massive reduction of interfacial frictional dissipation. We use a surface force balance to assess such dissipation at the sub-nanometer level, elucidating the mechanism involved, and atomic force microscopy to probe the NLGs structural stability. A useful proxy for the interfacial dissipation is the coefficient of friction, which remains as low as 10-4 at contact pressures at least up to 2 MPa, while under higher pressures exceeding the H-bonding energy density it increases abruptly and irreversibly to the still-low value 10-2. Under sustained sliding above this threshold, however, friction gradually decreases again, indicating recovery of the lubricating interface. Molecular dynamics simulations identify the compressive stress decrease due to hydrogen-bond rupture/rearrangement within the nanogel as a buried supramolecular transition associated with lubrication breakdown and recovery, while cargo release during sliding emphasizes the drug-delivery potential of such NLGs. These findings reveal how supramolecular core-shell reinforcement regulates load-bearing hydration lubrication, and provides a framework for designing adaptive biomimetic lubricants which are at the same time load-bearing intra-articular cargo-delivery vehicles.

The question, "How do these crystals grow?" is frequently asked but seldom answered. It remains a challenge, despite the power of modern analytical techniques. Molecular crystal formation can follow various pathways. Herein, observations of attachment of amorphous particles to the surfaces of a metal-organic framework (MOF) are presented. The attaching particles crystallize at the particle-MOF interface and merge with the growing crystal, leading to the eventual formation of smooth surfaces. The crystal edges exhibit faster attachment rates, while the centers grow more slowly, resulting in a highly unusual morphology. The nickel-based MOF presents a multidomain appearance with unexpected single crystallinity. Using a combined approach of correlative atomic force microscopy and scanning electron microscopy, it is found that the multidomain structure arises from varying growth rates at different regions of the crystals. The initial growth stages include step-edge growth on hexagonal MOF particles having smooth surfaces. This study sheds light on the growth mechanism of multidomain single crystals and the origin of their intricate morphologies.

Aqueous boundary lubrication depends critically on stable, hydrated interfacial layers, yet the role of molecular self-assembly in the tribological performance remains insufficiently understood. Here, we investigate a catanionic surfactant system, C12C3C12(SO3)2/CTAB, in which controlled variation of the gemini surfactant C12C3C12(SO3)2 molar fraction (Xg = 0.1, 0.2, 0.3) at a fixed total concentration of 2 mM drives structural transitions from spherical micelles to wormlike micelles and vesicles. Surface force balance and atomic force microscopy measurements reveal that all morphologies provide ultralow friction coefficients (10-3-10-4) via hydration lubrication but exhibit markedly different load-bearing capacities and mechanical stability. Spherical micelles provide the highest resilience and stability under pressures up to ∼70 atm; wormlike micelles display intermediate stability with partial structural damage under confinement; and vesicles yield the lowest friction (μ ≈ 10-4) but collapse at moderate pressures (15-30 atm). These findings demonstrate that aggregate morphology, controlled by stoichiometric charge neutralization, governs the balance between friction reduction and mechanical robustness, and highlight mixed surfactant self-assembly as an efficient strategy for low-concentration water-based lubricants.

Synovial joints achieve ultra-low friction through the cooperative interaction of multiple molecules. While hyaluronic acid (HA)-associated extracellular vesicles (EVs) are linked to osteoarthritis and boundary lubrication, their exact mechanistic role remains unclear. Here, a reductionist HA-phosphatidylcholine (HA-PC) complexes was introduced to mimic HA-EVs assemblies and unravel their structure-function relationships in joint lubrication. High-molecular-weight HA was mixed with representative gel-phase (hydrogenated soy PC, HSPC) and liquid-phase (1,2-dimyristoyl-sn‑glycero-3-phosphatidylcholine, DMPC; 1-palmitoyl-2-oleoyl-sn‑glycero-3-phosphatidylcholine, POPC) lipids. These results demonstrated that HA binding alters lipid assembly, increases their phase transition temperatures and promotes bilayer spreading upon interfacial contact. Furthermore, lipids disrupt the HA network which enhances its shear-thinning properties. Surface force balance measurements revealed ultralow friction μ∼ 10-5-10-3 that remains robust under high pressure for both HA-HSPC and HA-POPC complex. This study demonstrated the synergy provided by the HA-PC complex and may shed light to the role of synovial fluid HA-EVs as adaptive boundary lubricants, supporting a multicomponent model of synovial lubrication. STATEMENT OF SIGNIFICANCE: Synovial joints including hips and knees maintain ultralow friction - essential for joint health and for suppressing osteoarthritis (OA), a debilitating joint disease affecting millions - through synergistic interactions among multiple molecular constituents, among which extracellular vesicles (EVs) are believed prominent. Growing evidence shows that many EVs are physically associated with hyaluronic acid (HA); however, the mechanical consequences of this coupling, and its disruption in OA, remain unclear. Using a reductionist HA-phosphatidylcholine system that mimics core HA-EV interactions, we unravel their structure-function relationships in joint lubrication. Our results provide insight into how HA-EV assemblies may contribute to efficient pressure-resistant boundary lubrication, and how synovial fluid remodelling of HA in OA may drive lubrication failure and disease progression.

In this study, we employed traditional methods and deep learning models to improve resolution and quality of low-resolution AFM images made under standard ambient scanning. Both traditional methods and deep learning models were benchmarked and quantified regarding fidelity, quality, and a survey taken by AFM experts. The deep learning models outperform the traditional methods and yield better results. Additionally, some common AFM artifacts, such as streaking, are present in the ground truth high-resolution images. These artifacts are partially attenuated by the traditional methods but are completely eliminated by the deep learning models. This work shows deep learning models to be superior for super-resolution tasks and enables significant reduction in AFM measurement time, whereby low-pixel-resolution AFM images are enhanced in both resolution and fidelity through deep learning.

The extremely low sliding friction of articular cartilage in synovial joints has been attributed to phospholipid boundary layers, lubricating via the hydration lubrication mechanism at their exposed, highly hydrated polarhead-groups, in a medium - the synovial fluid - where osmolytes, which may modify the hydration layer, are ubiquitous. Here, using a surface force balance (SFB), we carried out a systematic study to elucidate the effect of sucrose, a known osmotic regulator solute, with concentrations csucrose, ranging from 5 to 20 wt%, on the normal and shear forces between interacting phosphatidylcholine (PC) bilayers, both in the gel (1,2-dipalmitoyl-snglycero-3-phosphocholine, DPPC) and liquid (1,2-dimyristoyl-sn-glycero-3-phosphocholine, DMPC) phases, supported on atomically-smooth mica substrates. Several additional approaches including cryo-transmission electron microscope, atomic force microscopy, small- and wide-angle X-ray scattering, differential scanning calorimetry, dynamic light scattering and zeta potential measurements are exploited to get additional insight into the nature of the sucrose-dependent interactions. As csucrose is varied, a remarkable variation in the friction is observed: a marked reduction in friction is seen at low csucrose, but at higher sucrose levels the friction increases, for both gel and liquid phase lipids. This challenges the expectation that hydration lubrication is degraded by osmotic solutes, due to their competing for water of hydration, and reveals for the first time a non-monotonic effect of a sugar on the interactions, particularly frictional forces, between lipid bilayers. This non-monotonic effect correlates with the bilayer potential, and is attributed to a concentration-dependent affinity of the sugar to the PC headgroups.

Lipid bilayers, ubiquitous in living systems, form lubricious boundary layers in aqueous media, with broad relevance for biolubrication, especially in mechanically stressed environments such as articular cartilage in joints, as well as for modifying material interfacial properties. Model studies have revealed efficient lubricity by single-component lipid bilayers; synovial joints, however (e.g. hips and knees), comprise over a hundred different lipids, raising the question of whether this is natural redundancy or whether it confers any lubrication benefits. Here, we examine lubrication by progressively more complex mixtures of lipids representative of those in joints, using a surface forces balance at physiologically relevant salt concentrations and pressures. We find that different combinations of such lipids differ very significantly in the robustness of the bilayers to hemifusion under physiological loads (when lubrication breaks down), indicating a clear lubrication synergy afforded by multiple lipid types in the bilayers. Insight into the origins of this synergy is provided by detailed molecular dynamics simulations of potential profiles for the formation of stalks, the essential precursors of hemifusion, between bilayers of the different lipid mixtures used in the experiments. These reveal how bilayer hemifusion—and thus lubrication breakdown—depends on the detailed lipid bilayer composition, through the corresponding separation into domains that are better able to resist stalk formation. Our results shed light on the role of lipid-type proliferation in biolubrication synergy, point to improved treatment modalities for common joint diseases such as osteoarthritis, and indicate how lipid-based interfacial modification in a materials context may be optimized.

Designing plant protein-based aqueous lubricants can be of great potential to achieve sustainability objectives by capitalising on inherent functional groups without using synthetic chemicals; however, such a concept remains in its infancy. Here, we engineer a class of self-assembled sustainable materials by using plant-based protofilaments and their assembly within a biopolymeric hydrogel giving rise to a distinct patchy architecture. By leveraging physical interactions, this material offers superlubricity with friction coefficients of 0.004-to-0.00007 achieved under moderate-to-high (102-to-103 kPa) contact pressures. Multiscale experimental measurements combined with molecular dynamics simulations reveal an intriguing synergistic mechanism behind such ultra-low friction - where the uncoated areas of the protofilaments glue to the surface by hydrophobic interactions, whilst the hydrogel offers the hydration lubrication. The current approach establishes a robust platform towards unlocking an untapped potential of using plant protein-based building blocks across diverse applications where achieving superlubricity and environmental sustainability are key performance indicators. Superlubricity is important for energy and biomedical applications but typical building blocks are limited to synthetically-sourced polymeric materials. Here, self-assembly of plant-based protofilaments in biopolymeric hydrogels were engineered offering superlubricity performance.

Healthy articular cartilage has excellent lubricating properties, with friction coefficients reaching extremely low values at physiological pressures. Such high-performing lubricating layer in joints is attributed to the surface hydration arising from the interplay between multiple hydrophilic biopolymers (such as hyaluronic acid, proteoglycans, and lubricin) and phospholipids in the cartilage matrix. Mimicking such molecular structure, hydrogels, composed of a hydrophilic polymer network, have the potential to replicate the lubricating feature and possibly replace natural cartilages. In this study, we have synthesized a poly(2-methacryloyloxyethyl phosphorylcholine-co-N-isopropylacrylamide) (PMPC-co-PNIPAM, PMN)random copolymer with highly-hydrated lubricious 2-methacryloyloxyethyl phosphorylcholine moieties and less hydrated N-isopropylacrylamide moieties. Incorporation of PMN copolymers within various hydrogels significantly reduces the gels sliding surface friction, resulting in low friction coefficients against different counter surfaces, including stainless steel (hard metal surface), polyethylene (hydrophobic surface), and polyHEMA (soft hydrogel surface). Additionally, hydrogels containing PMN are shown to be biocompatible and have excellent antifouling properties, making them an ideal coating for commercially available stents. With these qualities, hydrogels containing PMN stand out as a promising new material with numerous possible applications.

Transient electric fields across cell bilayer membranes can lead to electroporation and cell fusion, effects crucial to cell viability whose biological implications have been extensively studied. However, little is known about these behaviours in a materials context. Here we find that transmembrane electric fields can lead to a massive, reversible modulation of the sliding friction between surfaces coated with lipid-bilayer membranes-a 200-fold variation, up to two orders of magnitude greater than that achieved to date. Atomistic simulations reveal that the transverse fields, resembling those at cell membranes, lead to fully reversible electroporation of the confined bilayers and the formation of inter-bilayer bridges analogous to the stalks preceding intermembrane fusion. These increase the interfacial dissipation through reduced hydration at the slip plane, forcing it to revert in part from the low-dissipation, hydrated lipid-headgroup plane to the intra-bilayer, high-dissipation acyl tail interface. Our results demonstrate that lipid bilayers under transmembrane electric fields can have striking materials modification properties. Lipid bilayers under the influence of electric fields, similar to those across cell membranes, act as moderators of shear force between solid surfaces, presenting a new route to tuning interfacial properties across thin films.

Transient electric fields across cell bilayer membranes can lead to electroporation, as well as to cell fusion, and have been extensively studied. We find that transmembrane electric fields similar to those in cells can lead to a massive, reversible modulation--by up to 200-fold--of the interfacial energy dissipation between surfaces sliding across the lipid bilayer membranes. Atomistic simulations reveal that this arises from (fully reversible) electroporation of the interfacially-confined bilayers, and formation of bilayer bridges analogous to stalks preceding intermembrane fusion. These cell-membrane-mimicking effects topologically-force the slip to partially-revert from the low-dissipation, hydrated lipid-headgroups plane to the intra-bilayer, high-dissipation acyl tail interface. Our results demonstrate that lipid bilayers under transmembrane electric fields can have striking materials-modification properties, and shed new light on membrane hemifusion.

The very low sliding friction of articular cartilage in the major synovial joints such as hips and knees is crucial for their well-being, and has been attributed to lubrication by phospholipid boundary layers. While single-component lipid layers have demonstrated efficient lubricity in model studies, in living joints there is a large number of different lipids, raising the question of whether this is natural redundancy, or whether this multiplicity confers any benefits. Here we examine lubrication by progressively more complex mixtures of lipids representative of those in joints, using a surface forces balance at physiologically-relevant salt concentrations and pressures. We find that different lipid combinations differ very significantly in their lubricating ability, as manifested by their robustness to hemifusion under physiological loads, pointing to a clear lubrication synergy arising from multiple lipid types in the lubricating layers. Insight into the origins of this synergy is provided by molecular dynamics (MD) simulations of the different lipid mixtures used in the experiments, which directly reveal how hemifusion - associated with greatly increased friction - depends on the detailed lipid composition. Our results provide insight into the role of lipid type proliferation in healthy synovial joints, and point to new treatment modalities for osteoarthritis.

Phosphatidylcholine (PC) lipid bilayers at surfaces massively reduce sliding friction, via the hydration lubrication mechanism acting at their highly-hydrated phosphocholine headgroups, a central paradigm of biological lubrication, particularly at articular cartilage surfaces where low friction is crucial for joint well-being. Nanotribological measurements probed the effect on such lubrication of dehydration by dimethyl sulfoxide (DMSO), known to strongly dehydrate the phosphocholine headgroups of such PC bilayers, i.e. reduce the thickness of the inter-bilayer water layer, and thus expected to substantially degrade the hydration lubrication. Remarkably, and unexpectedly, we found that the dehydration has little effect on the friction. We used several approaches, including atomic force microscopy, small- and wide-angle X-ray scattering and all-atom molecular dynamics simulations to elucidate this. Our results show that while DMSO clearly removes hydration water from the lipid head-groups, this is offset by both higher areal head-group density and by rigidity-enhancement of the lipid bilayers, both of which act to reduce frictional dissipation. This sheds strong light on the robustness of lipid-based hydration lubrication in biological systems, despite the ubiquitous presence of bio-osmolytes which compete for hydration water.

The viscoelectric effect concerns the increase in viscosity of a polar liquid in an electric field due to its interaction with the dipolar molecules and was first determined for polar organic liquids more than 80 y ago. For the case of water, however, the most common polar liquid, direct measurement of the viscoelectric effect is challenging and has not to date been carried out, despite its importance in a wide range of electrokinetic and flow effects. In consequence, estimates of its magnitude for water vary by more than three orders of magnitude. Here, we measure the viscoelectric effect in water directly using a surface force balance by measuring the dynamic approach of two molecularly smooth surfaces with a controlled, uniform electric field between them across highly purified water. As the water is squeezed out of the gap between the approaching surfaces, viscous damping dominates the approach dynamics; this is modulated by the viscoelectric effect under the uniform transverse electric field across the water, enabling its magnitude to be directly determined as a function of the field. We measured a value for this magnitude, which differs by one and by two orders of magnitude, respectively, from its highest and lowest previously estimated values.

Regulating hydrogel actuators with chemical reaction networks is instrumental for constructing life-inspired smart materials. Herein, hydrogel actuators are engineered that are regulated by the autocatalytic front of thiols. The actuators consist of two layers. The first layer, which is regular polyacrylamide hydrogel, is in a strained conformation. The second layer, which is polyacrylamide hydrogel with disulfide crosslinks, maintains strain in the first layer. When thiols released by the autocatalytic front reduce disulfide crosslinks, the hydrogel actuates by releasing the mechanical strain in the first layer. The autocatalytic front is sustained by the reaction network, which uses thiouronium salts, disulfides of β-aminothiols, and maleimide as starting components. The gradual actuation by the autocatalytic front enables movements such as gradual unrolling, screwing, and sequential closing of "fingers." This actuation also allows the transmission of chemical signals in a relay fashion and the conversion of a chemical signal to an electrical signal. Locations and times of spontaneous initiation of autocatalytic fronts can be preprogrammed in the spatial distribution of the reactants in the hydrogel. To approach the functionality of living matter, the actuators triggered by an autocatalytic front can be integrated into smart materials regulated by chemical circuits.

Boundary lubrication is associated with two sliding molecularly thin lubricated film-coated surfaces, where the energy dissipation occurs at the slip-plane between lubricated films. The hydration lubrication paradigm, which accounts for ultralow friction in aqueous media, has been extended to various systems, with phosphatidylcholine (PC) lipids recognized as extremely efficient lubrication elements due to their high hydration level. In this work, we extend a previous study (Lin et al., Langmuir 35 (2019) 6048-6054), where a charged lipid-poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) conjugate was prepared, to the very different case of a neutral lipid-PMPC) conjugate. This neutral molecule stabilizes the liposomes by attaching highly water-soluble PMPC to the surface of liposomes with its lipid moieties incorporated in the lipid bilayers. Such neutral polyphosphocholinated liposomes provide a surface lubricity which is well within the superlubrication regime (coefficient of friction = ca. 10-3 or even lower). In contrast, negatively charged lipid/polyphosphocholine conjugates modified liposomes were unable to adsorb on negatively-charged (mica) surfaces. Our method provides stable liposomes that can adsorb on negatively charged surfaces and provide superlubricity.

Duncan Dowson, whom this issue commemorates, was a world leader in the field of biotribology, with prolific contributions both in fluid-based and boundary lubrication of biological tissues, in particular articular cartilage, a central issue in biotribology due to its importance for joint homeostasis. Here we explore further the issue of cartilage boundary lubrication, which has been attributed to phospholipid (PL)-exposing layers at the cartilage surface in part. A surface force balance (SFB) with unique sensitivity is used to investigate the normal and frictional interactions of the boundary layers formed by PLs extracted from osteoarthritic (OA) human synovial fluid (hSF). Our results reveal that vesicles of the OA-hSF lipids rupture spontaneously to form bilayers on the mica substrate (which, like the in-vivo articular cartilage surface in synovial joints, is negatively-charged) which then undergo hemifusion at quite low pressures in the SFB, attributed to the large heterogeneity of the hSF lipids. Nanometric friction measurements reveal friction coefficients mu = ca. 0.03 across the hemi-fused bilayer of these lipids, indicating residual hydration lubrication at the lipid-headgroup vs. substrate interface. Addition of calcium ions causes an increase in friction to mu = ca. 0.2, attributed either to calcium-bridging attraction of lipid headgroups to the negatively-charged substrate, or a shift of the slip plane to the more dissipative hydrophobic-tail vs. hydrophobic-tail interface. Our results suggest that the heterogeneity and composition of the OA-hSF lipids may be associated with higher friction at the cartilage boundary layers, and thus a connection with greater wear and degradation, due to hemifusion of the exposed lipid bilayers.

Phosphatidylcholine lipid bilayers or liposomes at interfaces in aqueous environments can provide extremely efficient lubrication. This is attributed to the hydration lubrication mechanism acting at the highly hydrated phosphocholine-headgroup layers exposed at the outer surface of each bilayer. Micelles exposing such phosphocholine groups could be an attractive alternative to liposomes due to their much easier preparation and structure control, but all studies to date of surfactant micelles have revealed that at relatively low normal stresses the surface layers rupture and friction increases abruptly. Here, we examine surface interactions between three kinds of phosphocholine-exposing micelles with different designed structures: single-tail surfactant micelles, homo-oligomeric micelles, and block copolymer micelles. Normal and shear forces between mica surfaces immersed in solutions of these micelles were measured using a surface force balance. The adsorbed layers on the mica were imaged using atomic force microscope, revealing surface structures ranging from wormlike to spherical micelles. The block copolymer micelles showed relatively low coverage arising from their stabilizing corona and consequently poor lubrication (μ ∼ 10–1). In contrast, the surfactant and homo-oligomeric micelles fully covered the mica surface and demonstrated excellent lubrication (μ ∼ O(10–3)). However, while the boundary layer of single-tailed surfactant micelles degraded under moderate pressure, the homo-oligomeric micellar boundary layer was robust at all applied contact pressures in our study (up to about 5 MPa). We attribute the difference to the much greater energy required to remove a homo-oligomeric molecule from its micelle, resulting in far greater stability under pressure and shear.

Phospholipid–macromolecule complexes have been proposed to form highly efficient, lubricating boundary layers at artificial soft surfaces or at biological surfaces such as articular cartilage, where the friction reduction is attributed to the hydration lubrication mechanism acting at the exposed, hydrated head groups of the lipids. Here we measure, using a surface force balance, the normal and frictional interactions between model mica substrates across several different configurations of phosphatidylcholine (PC) lipid aggregates and adsorbed polymer (PEO) layers, to provide insight into the nature of such lubricating boundary layers in both symmetric and especially asymmetric configurations. Our results reveal that, irrespective of the configuration, the slip plane between the sliding surfaces reverts wherever possible to a bilayer–bilayer interface where hydration lubrication reduces the friction strongly. Where such an interface is not available, the sliding friction remains high. These findings may account for the low friction observed between both biological and synthetic hydrogel surfaces which may be asymmetrically coated with lipid-based boundary layers and fully support the hydration lubrication mechanism attributed to act at such boundary layers.

The lubrication of hydrogels arises from fluid or solvated surface phases. By contrast, the lubricity of articular cartilage, a complex biohydrogel, has been at least partially attributed to nonfluid, lipid-exposing boundary layers. We emulated this behavior in synthetic hydrogels by incorporating trace lipid concentrations to create a molecularly thin, lipid-based boundary layer that renews continuously. We observed a 80% to 99.3% reduction in friction and wear relative to the lipid-free gel, over a wide range of conditions. This effect persists when the gels are dried and then rehydrated. Our approach may provide a method for sustained, extreme lubrication of hydrogels in applications from tissue engineering to clinical diagnostics.