Insight into the assembly of lipid-hyaluronan complexes in osteoarthritic conditions.

Interactions between molecules in the synovial fluid and the cartilage surface may play a vital role in the formation of adsorbed films that contribute to the low friction of cartilage boundary lubrication. Osteoarthritis (OA) is the most common degenerative joint disease. Previous studies have shown that in OA-diseased joints, hyaluronan (HA) not only breaks down resulting in a much lower molecular weight (MW), but also its concentration is reduced ten times. Here, we have investigated the structural changes of lipid-HA complexes as a function of HA concentration and MW to simulate the physiologically relevant conditions that exist in healthy and diseased joints. Small angle neutron scattering and dynamic light scattering were used to determine the structure of HA-lipid vesicles in bulk solution, while a combination of atomic force microscopy and quartz crystal microbalance was applied to study their assembly on a gold surface. We infer a significant influence of both MW and HA concentrations on the structure of HA-lipid complexes in bulk and assembled on a gold surface. Our results suggest that low MW HA cannot form an amorphous layer on the gold surface, which is expected to negatively impact the mechanical integrity and longevity of the boundary layer and could contribute to the increased wear of the cartilage that has been reported in joints diseased with OA.

SANS characterization of time dependent, slow molecular exchange in an SDS micellar system.

We have investigated the molecular exchange of sodium dodecyl sulfate (SDS) micelles in aqueous solution by time-resolved small angle neutron scattering (TR-SANS) measurements as a function of the surfactant and salt concentration. Starting with deuterated (d-SDS) and protonated (h-SDS) SDS micelles, surfactant exchange across the micelles leads to a randomized distribution of d-SDS and h-SDS within each micelle. By employing the contrast matching technique, we have studied this randomization process which is a direct measure of the molecular exchange of this system. Our results show that the randomization of the pure h-SDS and d-SDS micelles occurs in two steps: first, an almost instantaneous drop in the scattering intensity is observed where ∼80% of the micelles are randomized (contrast matched). After this, micelle randomization progresses slowly spanning over ∼100 hours. Importantly, we show that the kinetics in the second step are dominated by the formation of domains rich in either h-SDS, d-SDS and randomized (50 : 50 h-SDS : d-SDS). The slow exchange step is modeled via a phenomenological approach by drawing analogy to the Langmuir adsorption theory. Finally, the effects of the surfactant and salt concentrations on the instantaneous, and the time dependent randomization of SDS micelles are discussed.

Pathological cardiolipin-promoted membrane hemifusion stiffens pulmonary surfactant membranes.

Lower tract respiratory diseases such as pneumonia are pervasive, affecting millions of people every year. The stability of the air/water interface in alveoli and the mechanical performance during the breathing cycle are regulated by the structural and elastic properties of pulmonary surfactant membranes (PSMs). Respiratory dysfunctions and pathologies often result in, or are caused by, impairment of the PSMs. However, a gap remains between our knowledge of the etiology of lung diseases and the fundamental properties of PSMs. For example, bacterial pneumonia in humans and mice has been associated with aberrant levels of cardiolipin, a mitochondrial-specific, highly unsaturated 4-tailed anionic phospholipid, in lung fluid, which likely disrupts the structural and mechanical integrity of PSMs. Specifically, cardiolipin is expected to significantly alter PSM elasticity due to its intrinsic molecular properties favoring membrane folding away from a flat configuration. In this paper, we investigate the structural and mechanical properties of the lipidic components of PSMs using lipid-based models as well as bovine extracts affected by the addition of pathological cardiolipin levels. Specifically, using a combination of optical and atomic force microscopy with a surface force apparatus, we demonstrate that cardiolipin strongly promotes hemifusion of PSMs and that these local membrane contacts propagate at larger scales, resulting in global stiffening of lung membranes.

Correction: Nanoscale insight into the degradation mechanisms of the cartilage articulating surface preceding OA.

Correction for 'Nanoscale insight into the degradation mechanisms of the cartilage articulating surface preceding OA' by Tooba Shoaib, et al., Biomater. Sci., 2020, 8, 3944-3955, DOI: 10.1039/D0BM00496K.

Nanoscale insight into the degradation mechanisms of the cartilage articulating surface preceding OA.

Osteoarthritis (OA) is a degenerative joint disease and a leading cause of disability globally. In OA, the articulating surface of cartilage is compromised by fissures and cracks, and sometimes even worn away completely. Due to its avascular nature, articular cartilage has a poor self-healing ability, and therefore, understanding the mechanisms underlying degradation is key for OA prevention and for optimal design of replacements. In this work, the articulating surface of bovine cartilage was investigated in an environment with enhanced calcium concentration -as often found in cartilage in relation to OA- by combining atomic force microscopy, spectroscopy and an extended surface forces apparatus for the first time. The experimental results reveal that increased calcium concentration irreversibly weakens the cartilage's surface layer, and promotes stiction and high friction. The synergistic effect of calcium on altering the cartilage surface's structural, mechanical and frictional properties is proposed to compromise cartilage integrity at the onset of OA. Furthermore, two mechanisms at the molecular level based on the influence of calcium on lubricin and on the aggregation of the cartilage's matrix, respectively, are identified. The results of this work might not only help prevent OA but also help design better cartilage replacements.

Influence of Loading Conditions and Temperature on Static Friction and Contact Aging of Hydrogels with Modulated Microstructures.

Biological tribosystems enable diverse functions of the human body by maintaining extremely low coefficients of friction via hydrogel-like surface layers and a water-based lubricant. Although stiction has been proposed as a precursor to damage, there is still a lack of knowledge about its origin and its relation to the hydrogel's microstructure, which impairs the design of soft matter as replacement biomaterials. In this work, the static friction of poly(acrylamide) hydrogels with modulated composition was investigated by colloidal probe lateral force microscopy as a function of load, temperature, and loading time. Temperature-dependent studies enable to build a phase diagram for hydrogel's static friction, which explains stiction via (polymer) viscoelastic and poroelastic relaxation, and a subtle transition from solid- to liquid-like interfacial behavior. At room temperature, the static friction increases with loading time, a phenomenon called contact aging, which stems from the adhesion of the polymer to the colloid and from the drainage-induced increase in contact area. Contact aging is shown to gradually vanish with increase in temperature, but this behavior strongly depends on the hydrogel's composition. This work scrutinizes the relation between the microstructure of hydrogel-like soft matter and interfacial behavior, with implications for diverse areas of inquiry, not only in biolubrication and biomedical applications but also in soft robotics and microelectromechanical devices, where the processes occurring at the migrating hydrogel interface are of relevance. The results support that modulating both the hydrogel's mesh size and the structure of the near-surface region is a means to control static friction and adhesion. This conceptual framework for static friction will foster further understanding of the wear of hydrogel-like materials.

Stick-Slip Friction Reveals Hydrogel Lubrication Mechanisms.

The lubrication behavior of the hydrated biopolymers that constitute tissues in organisms differs from that outlined by the classical Stribeck curve, and studying hydrogel lubrication is a key pathway to understand the complexity of biolubrication. Here, we have investigated the frictional characteristics of polyacrylamide (PAAm) hydrogels with various acrylamide concentrations, exhibiting Young's moduli (E) that range from 1 to 40 kPa, as a function of applied normal load and sliding velocities by colloid probe lateral force microscopy. The speed-dependence of the friction force shows an initial decrease in friction with increasing velocity, while, above a transition velocity V*, friction increases with speed. This study reveals two different boundary lubrication mechanisms characterized by distinct scaling laws. An unprecedented and comprehensive study of the lateral force loops reveals intermittent friction or stick-slip above and below V*, with characteristics that depend on the hydrogel network, applied load, and sliding velocity. Our work thus provides insight into the closely tied parameters governing hydrogel lubrication mechanisms, and stick-slip friction.

Self-adaptive hydrogels to mineralization.

Mineralized biological tissues, whose behavior can range from rigid to compliant, are an essential component of vertebrates and invertebrates. Little is known about how the behavior of mineralized yet compliant tissues can be tuned by the degree of mineralization. In this work, a synthesis route to tune the structure and mechanical response of agarose gels via ionic crosslinking and mineralization has been developed. A combination of experimental techniques demonstrates that crosslinking via cooperative hydrogen bonding in agarose gels is disturbed by calcium ions, but they promote ionic crosslinking that modifies the agarose network. Further, it is shown that the rearrangement of the hydrogel network helps to accommodate precipitated minerals into the network -in other words, the hydrogel self-adapts to the precipitated mineral- while maintaining the viscoelastic behavior of the hydrogel, despite the reinforcement caused by mineralization. This work not only provides a synthesis route to design biologically inspired soft composites, but also helps to understand the change of properties that biomineralization can cause to biological tissues, organisms and biofilms.

Assembly, Morphology, Diffusivity, and Indentation of Hydrogel-Supported Lipid Bilayers.

Recognizing the limitations of solid-supported lipid bilayers to reproduce the behavior of cell membranes, including bendability, transmembrane protein inclusion, and virus entry, this study describes a novel biomimetic system for cell membranes with the potential to overcome these and other limitations. The developed strategy utilizes a hydrogel with tunable mechanical behavior that resembles those of living cells as the soft support for the phospholipid bilayer, while a polyelectrolyte multilayer film serves as an intermediate layer to facilitate the self-assembly of the lipid bilayer on the soft cushion. Quartz crystal microbalance studies show that, upon coming into contact with the polyelectrolyte film, vesicles fuse and rupture to yield a robust lipid bilayer. Fluorescence recovery after photobleaching confirms the formation of a membrane, while atomic force microscopy shows a low adhesion between the indenting probe and the bilayer. More importantly, in comparison to the solid-supported lipid bilayer, the response of this biomimetic system to nanoindentation demonstrates its increased mechanical stability and bendability when assembled on a soft cushion. Hence, the developed hydrogel-supported lipid bilayers can mimic biomechanical properties of cell membranes, which will enable scientists to study and to understand biophysicochemical interactions between cell membranes and extracellular entities.