arXiv subjects

Jacob Klein

Publications and source records attributed to Jacob Klein.

16 recordsLinked to original sources

arXiv2024

The Effects of Splayed Lipid Molecules on Lubrication by Lipid Bilayers

The outstanding lubrication of articular cartilage in the major synovial joints such as hips and knees, essential for the joint well-being, has been attributed to boundary layers of lipids at the outer cartilage surfaces, which have very low friction mediated by the hydration lubrication mechanism at their highly hydrated exposed headgroups. However, the role of spontaneously present lipid splays, lipids with an acyl tail in each of the opposing bilayers, in modulating the frictional force between lipid bilayers has not, to date, been considered. In this study, we perform all-atom molecular dynamics simulations to quantitatively assess the significance of splayed molecules within the framework of lubricating lipid bilayers. We demonstrate that, although transient, splayed molecules significantly increase the inter-membrane friction until their retraction back into the lamellar phase, with this effect more steadily occurring at lower sliding velocities that are comparable to the physiological velocities of sliding articular cartilage.

cond-mat.soft↗

arXiv2024

Bioinspired polymer-incorporating self-lubricating and antifouling hydrogels

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.

cond-mat.soft↗

arXiv2024

Pressure-dependent adhesion between solid-supported PC-lipid bilayers and vesicles under electric fields

Fusion of lipid bilayers in membranes is important in processes from vesicle-cell interactions (as in drug delivery) to exosome-cell signaling, while transient transmembrane electric fields are known to occur spontaneously. Two contacting phosphatidylcholine (PC) lipid membranes are known to fuse into one under external electric fields, suggesting that the interaction between them is modified by the field as they approach, prior to the fusion event. Here we measure directly the adhesion energy between dimyristoylphosphatidylcholine (DMPC) and between distearoylphosphatidylcholine (DSPC) surface layers attached to solid substrates both without and with a transmembrane electric field. We find a marked pressure-dependent adhesion behavior in the electric field, which we attribute to fusion intermediates that are formed, shedding new light on membrane electro-fusion.

cond-mat.soft↗

arXiv2023

Liposomic lubricants suppress shear-stress induced inflammatory gene regulation in the joint in vivo

Osteoarthritis (OA) is a widespread, debilitating joint disease associated with articular cartilage degradation. It is driven via mechano-inflammatory catabolic pathways, presumed up-regulated due to increased shear stress on the cartilage-embedded chondrocytes, that lead to tissue degeneration. Here we demonstrate that the up-regulation of the matrix metalloproteinase 3 (Mmp3) and interleukin-1beta (Il1b) genes upon surgical joint destabilization in a model of murine OA is completely suppressed when lipid-based lubricants are injected into the joints. At the same time, Timp1, a compression but not shear-stress sensitive gene, is unaffected by lubricant. Our results provide direct evidence that biolubrication couples to catabolic gene regulation in OA, shed strong light on the nature of the chondrocytes' response to shear stress, and have clear implications for novel OA treatments.

physics.bio-ph↗

arXiv2023

Recent progress in cartilage lubrication

Healthy articular cartilage, covering the ends of bones in major joints such as hips and knees, presents the most efficiently-lubricated surface known in nature, with friction coefficients as low as 0.001 up to physiologically high pressures. Such low friction is indeed essential for its well being. It minimizes wear-and-tear and hence the cartilage degradation associated with osteoarthritis, the most common joint disease, and, by reducing shear stress on the mechanotransductive, cartilage-embedded chondrocytes (the only cell type in the cartilage), it regulates their function to maintain homeostasis. Understanding the origins of such low friction of the articular cartilage, therefore, is of major importance in order to alleviate disease symptoms, and slow or even reverse its breakdown. This progress report considers the relation between frictional behavior and the cellular mechanical environment in the cartilage, then reviews the mechanism of lubrication in the joints, in particular focusing on boundary lubrication. Following recent advances based on hydration lubrication, a proposed synergy between different molecular components of the synovial joints, acting together in enabling the low friction, has been proposed. Additionally, recent development of natural and of bio-inspired lubricants is reviewed.

physics.med-ph↗

arXiv2023

Effect of cholesterol on the mechanical stability of gel-phase phospholipid bilayers studied by AFM force spectroscopy

The low sliding friction of articular cartilage in the major joints , which is crucial for its homeostasis and for joint health, has been attributed to lipid bilayers forming lubricious boundary layers at its surface. The robustness of such layers, and thus their lubrication efficiency at joint pressures, depends on the lipids forming them, including cholesterol, which may act to strengthen of weaken the bilayer. A systematic study using an Atomic Force Microscope (AFM) was carried out to understand the effect of cholesterol on the nanomechanical stability of two saturated phospholipids, DSPC (1,2-distearoyl-sn-glycero-3-phosphatidlycholine) and DPPC (1,2-dipalmitoyl-sn-glycero-phosphatidylcholine), that differ in acyl chain lengths. Measurements were carried out both in water and in phosphate buffer solution (PBS). The nanomechanical stability of the lipid bilayers was quantitatively evaluated by measuring the breakthrough force needed to puncture the bilayer by the AFM tip. The molar fractions of cholesterol incorporated in the bilayers were 10% and 40%. We found that for both DSPC and DPPC, cholesterol significantly decreases the mechanical stability of the bilayers in solid ordered (SO) phase. In accordance with the literature, the strengthening effect of salt on the lipid bilayers was also observed. For DPPC with 10 mol % cholesterol, the effect of tip properties and the experimental procedure parameters on the breakthrough forces were also studied. Tip radius (2 - 42 nm), material (Si, Si3N4, Au) and loading rate (40 - 1000 nm/s) were varied systematically. The values of the breakthrough forces measured were not significantly affected by any of these parameters, showing that the weakening effect of cholesterol does not result from such changes in experimental conditions. This study helps to shed light on the mechanism of physiological lubrication.

cond-mat.soft↗

arXiv2023

Cell-inspired, massive electromodulation of interfacial energy dissipation

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.

cond-mat.mtrl-sci↗

arXiv2023

Multi-lipid synergy in synovial lubrication: natural redundancy vs. natural selection

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.

cond-mat.mtrl-sci↗

arXiv2023

Electric-field-induced topological changes in multilamellar and in confined lipid membranes

It is well known that lipid membranes respond to a threshold transmembrane electric field through a reversible mechanism called electroporation, where hydrophilic water pores form across the membrane, an effect widely used in biological systems. The effect of such fields on interfacially-confined (stacked or supported) lipid membranes, on the other hand, which may strongly modulate interfacial properties, has not to our knowledge been previously studied. Motivated by recent surface forces experiments showing a striking effect of electric fields on lubrication by confined lipid bilayers, we carried out all-atom molecular dynamics simulations of such membranes under transverse electric fields. We find that in addition to electroporation, a new feature emerges of locally merged bilayers which act to bridge the confining interfaces. These features shed light on the remodelling of confined lipid membrane stacks by electric fields, and provides insight into how such fields may modulate frictional and more generally surface interactions in the presence of lipid-based boundary layers.

cond-mat.soft↗

arXiv2023

Tuning energy dissipation via topologically electro-convoluted lipid-membrane boundary layers

It was recently discovered that friction between surfaces bearing phosphatidylcholine (PC) lipid bilayers can be increased by two orders of magnitude or more via an externally-applied electric field, and that this increase is fully reversible when the field is switched off. While this striking effect holds promising application potential, its molecular origin remains unknown due to difficulty in experimentally probing confined membrane structure at a molecular level. Our earlier molecular dynamics simulations revealed the equilibrium electroporated structure of such confined lipid membranes under an electric field; here we extend this approach to study the associated sliding friction between two solid surfaces across such PC bilayers. We identify the enhanced friction in the field as arising from membrane undulations due to the electroporation; this leads to some dehydration at the lipid-water interfaces, leading to closer contact and thus increased attraction between the zwitterionic headgroups, which results in increased frictional dissipation between the bilayers as they slide past each other. Additionally, the electric field facilitates formation of lipid bridges spanning the intersurface gap; at the sliding velocities of the experiments, these bridges increase the friction by topologically-forcing the slip-plane to pass through the acyl tail-tail interface, associated with higher dissipation during sliding. Our results account quantitatively for the experimentally-observed electro-modulated friction with boundary lipid bilayers, and indicate more generally how they may affect interactions between contacting surfaces, where high local transverse fields may be ubiquitous.

cond-mat.soft↗

arXiv2022

Neutral polyphosphocholine-modified liposomes as boundary superlubricants

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.

cond-mat.soft↗

arXiv2022

Interactions Between Bilayers of Phospholipids Mixture Extracted from Human Osteoarthritic Synovial Fluid

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.

cond-mat.soft↗

arXiv2022

Lipids and lipid-mixtures in boundary layers: from hydration lubrication to osteoarthritis

The hydration layer surrounding the phosphocholine headgroups of single-component phosphatidylcholine (PC) lipids, or of lipid-mixtures, assembled at an interface greatly modifies the interfacial properties and interactions. As water molecules within the hydration layer are held tightly by the headgroup but are nonetheless very fluid upon shear, the boundary lipid layers, exposing the highly hydrated headgroup arrays, can provide efficient boundary lubrication when sliding against an opposing surface, at physiologically-high contact pressures. Additionally, any free lipids in the surrounding liquid can heal defects which may form during sliding on the boundary PC layer. Similar boundary lipid layers contribute to the lubricating, pressure-bearing, and wear-protection functions of healthy articular joints. This review presents a survey of the relationship between the molecular composition of the interfacial complex and the lubrication behavior of the lipid-based boundary layers, which could be beneficial for designing boundary lubricants for intra-articular injection for the treatment of early OA.

cond-mat.soft↗

arXiv2019

Automated Classification of Helium Ingress in Irradiated X-750

Imaging nanoscale features using transmission electron microscopy is key to predicting and assessing the mechanical behavior of structural materials in nuclear reactors. Analyzing these micrographs is often a tedious and labour intensive manual process. It is a prime candidate for automation. Here, a region-based convolutional neural network is adapted to detect helium bubbles in micrographs of neutron-irradiated Inconel X-750 reactor spacer springs. We demonstrate that this neural network produces analyses of similar accuracy and reproducibility to that produced by humans. Further, we show this method as being four orders of magnitude faster than manual analysis allowing for generation of significant quantities of data. The proposed method can be used with micrographs of different Fresnel contrasts and magnification levels.

physics.app-ph↗

arXiv2011

Long-ranged attraction between disordered heterogeneous surfaces

Long-ranged attractions across water between two surfaces that are randomly covered with (mobile) positive and negative charge domains have been attributed to induced correlation of the charges (positive lining up with negative) as the surfaces approach. Here we show, by directly measuring normal forces under a rapid shear field, that these attractions may not in fact be due to such correlations. It is rather the inherent interaction-asymmetry between equally- and between oppositely-charged domains that results in the long-ranged attraction even in the complete absence of any charge correlation.

cond-mat.soft↗

arXiv2002

The polymer mat: Arrested rebound of a compressed polymer layer

Compression of an adsorbed polymer layer distorts its relaxed structure. Surface force measurements from different laboratories show that the return to this relaxed structure after the compression is released can be slowed to the scale of tens of minutes and that the recovery time grows rapidly with molecular weight. We argue that the arrested state of the free layer before relaxation can be described as a Guiselin brush structure1, in which the surface excess lies at heights of the order of the layer thickness, unlike an adsorbed layer. This brush structure predicts an exponential falloff of the force at large distance with a decay length that varies as the initial compression distance to the 6/5 power. This exponential falloff is consistent with surface force measurements. We propose a relaxation mechanism that accounts for the increase in relaxation time with chain length.

physics.chem-ph↗