Rotational and translational drags of a Janus particle close to a wall and a lipid membrane.

HYPOTHESIS: Measuring rotational and translational Brownian motion of single spherical particles reveals dissipations due to the interaction between the particle and the environment. EXPERIMENTS: In this article, we show experiments where the in-plane translational and the two rotational drag coefficients of a single spherical Brownian particle can be measured. These particle drags are functions of the particle size and of the particle-wall distance, and of the viscous dissipations at play. We measure drag coefficients for Janus particles close to a solid wall and close to a lipid bilayer membrane. FINDINGS: For a particle close to a wall, we show that according to hydrodynamic models, particle-wall distance and particle size can be determined. For a particle partially wrapped by lipid membranes, in absence of strong binding interactions, translational and rotational drags are significantly larger than the ones of non-wrapped particles. Beside the effect of the membrane viscosity, we show that dissipations in the deformed membrane cap region strongly contribute to the drag coefficients.

Stress overshoot, hysteresis, and the Bauschinger effect in sheared dense colloidal suspensions.

The mechanical nonlinear response of dense Brownian suspensions of polymer gel particles is studied experimentally and by means of numerical simulations. It is shown that the response to the application of a constant shear rate depends on the previous history of the suspension. When the flow starts from a suspension at rest, it exhibits an elastic response followed by a stress overshoot and then a plastic flow regime. Conversely, after flow reversal, the stress overshoot does not occur, and the apparent elastic modulus is reduced while numerical simulations reveal that the anisotropy of the local microstructure is delayed relative to the macroscopic stress.

Coarse-grained description of monounsaturated peroxidized phospholipid bilayers.

Lipid peroxides result from a reaction between cis-unsaturated lipid chains and singlet oxygen molecules leading to the addition of a peroxide OOH side group next to the acyl-chain double bond. It is now established that HP-POPC (hydroperoxidized POPC) molecules form stable, thin, and laterally expanded bilayers. The difference in the structural organization arises from the hydrophilic character of the OOH side group that has a strong affinity with the water interface region, leading to significant reorganization of the bilayer. In this article, we describe a coarse-grained (CG) model of POPC and DOPC lipid peroxides within the framework of the Martini CG force-field (v2.2), derived from experimental data. We then discuss extensively the predicted structure and the influence of hydration and show how shifting the position of the unsaturated bonds along the chain changes the structure. Finally, we provide electron and neutron scattering length density profiles of the simulated bilayers.

Perturbing the catenoid: Stability and mechanical properties of nonaxisymmetric minimal surfaces.

Minimal surface problems arise naturally in many soft matter systems whose free energies are dominated by surface or interface energies. Of particular interest are the shapes, stability, and mechanical stresses of minimal surfaces spanning specific geometric boundaries. The "catenoid" is the best-known example where an analytical solution is known which describes the form and stability of a minimal surface held between two parallel, concentric circular frames. Here we extend this problem to nonaxisymmetric, parallel frame shapes of different orientations by developing a perturbation approach around the known catenoid solution. We show that the predictions of the perturbation theory are in good agreement with experiments on soap films and finite element simulations (Surface Evolver). Combining theory, experiment, and simulation, we analyze in depth how the shapes, stability, and mechanical properties of the minimal surfaces depend on the type and orientation of elliptic and three-leaf clover shaped frames. In the limit of perfectly aligned nonaxisymmetric frames, our predictions show excellent agreement with a recent theory established by Alimov et al. [Phys. Fluids 33, 052104 (2021)1070-663110.1063/5.0047461]. Moreover, we put in evidence the intriguing capacity of minimal surfaces between nonaxisymmetric frames to transmit a mechanical torque despite being completely liquid. These forces could be interesting to exploit for mechanical self-assembly of soft matter systems or as highly sensitive force captors.

Rheology of sliding leaflets in coarse-grained DSPC lipid bilayers.

Amphiphilic lipid bilayers modify the friction properties of the surfaces on top of which they are deposited. In particular, the measured sliding friction coefficient can be significantly reduced compared with the native surface. We investigate in this work the friction properties of a numerical coarse-grained model of DSPC (1,2-distearoyl-sn-glycero-3-phosphocholine) lipid bilayer subject to longitudinal shear. The interleaflet friction coefficient is obtained from out-of-equilibrium pulling or from relaxation simulations. In particular, we gain access to the transient viscoelastic response of a sheared bilayer. The bilayer mechanical response is found to depend significantly on the membrane physical state, with evidence in favor of a linear response regime in the fluid but not in the gel region. The linear response validity domain is established, and the timescales appearing in the membrane response discussed.

Ripple-like instability in the simulated gel phase of finite size phosphocholine bilayers.

Atomistic molecular dynamics simulations have reached a degree of maturity that makes it possible to investigate the lipid polymorphism of model bilayers over a wide range of temperatures. However if both the fluid Lα and tilted gel [Formula: see text] states are routinely obtained, the [Formula: see text] ripple phase of phosphatidylcholine lipid bilayers is still unsatifactorily described. Performing simulations of lipid bilayers made of different numbers of DPPC (1,2-dipalmitoylphosphatidylcholine) molecules ranging from 32 to 512, we demonstrate that the tilted gel phase [Formula: see text] expected below the pretransition cannot be obtained for large systems (equal or larger than 94 DPPC molecules) through common simulations settings or temperature treatments. Large systems are instead found in a disordered gel phase which display configurations, topography and energies reminiscent from the ripple phase [Formula: see text] observed between the pretransition and the main melting transition. We show how the state of the bilayers below the melting transition can be controlled and depends on thermal history and conditions of preparations. A mechanism for the observed topographic instability is suggested.

Molecular organization in hydroperoxidized POPC bilayers.

Lipid hydroperoxides are the primary reaction products of lipid oxidation, a natural outcome of life under oxygen. While playing a major role in cell metabolism, the microscopic origins of the effects of lipid hydroperoxidation on biomembranes remain elusive. Here we probe the polar structure of partially to fully hydroperoxidized bilayers of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) by a combination of environment-sensitive fluorescent probes and coarse-grained Martini numerical simulations. We find that the inserted organic hydroperoxide group -OOH migrates preferentially to the surface for bilayers with small fractions of hydroperoxidized lipids, but populates also significantly the bilayer interior for larger fractions. Our findings suggest that by modifying the intimate polarity of biomembranes, lipid peroxidation will have a significant impact on the activity of transmembrane proteins and on the bio-medical efficiency of membrane active molecules such as cell-penetrating and antimicrobial peptides.

MLLPA: A Machine Learning-assisted Python module to study phase-specific events in lipid membranes.

Machine Learning-assisted Lipid Phase Analysis (MLLPA) is a new Python 3 module developed to analyze phase domains in a lipid membrane based on lipid molecular states. Reading standard simulation coordinate and trajectory files, the software first analyze the phase composition of the lipid membrane by using machine learning tools to label each individual molecules with respect to their state, and then decompose the simulation box using Voronoi tessellations to analyze the local environment of all the molecules of interest. MLLPA is versatile as it can read from multiple format (e.g., GROMACS, LAMMPS) and from either all-atom (e.g., CHARMM36) or coarse-grain models (e.g., Martini). It can also analyze multiple geometries of membranes (e.g., bilayers, vesicles). Finally, the software allows for training with more than two phases, allowing for multiple phase coexistence analysis.

Accumulation of styrene oligomers alters lipid membrane phase order and miscibility.

Growth of plastic waste in the natural environment, and in particular in the oceans, has raised the accumulation of polystyrene and other polymeric species in eukyarotic cells to the level of a credible and systemic threat. Oligomers, the smallest products of polymer degradation or incomplete polymerization reactions, are the first species to leach out of macroscopic or nanoscopic plastic materials. However, the fundamental mechanisms of interaction between oligomers and polymers with the different cell components are yet to be elucidated. Simulations performed on lipid bilayers showed changes in membrane mechanical properties induced by polystyrene, but experimental results performed on cell membranes or on cell membrane models are still missing. We focus here on understanding how embedded styrene oligomers affect the phase behavior of model membranes using a combination of scattering, fluorescence, and calorimetric techniques. Our results show that styrene oligomers disrupt the phase behavior of lipid membranes, modifying the thermodynamics of the transition through a spatial modulation of lipid composition.

A machine learning study of the two states model for lipid bilayer phase transitions.

We have adapted a set of classification algorithms, also known as machine learning, to the identification of fluid and gel domains close to the main transition of dipalmitoyl-phosphatidylcholine (DPPC) bilayers. Using atomistic molecular dynamics conformations in the low and high temperature phases as learning sets, the algorithm was trained to categorise individual lipid configurations as fluid or gel, in relation with the usual two-states phenomenological description of the lipid melting transition. We demonstrate that our machine can learn and sort lipids according to their most likely state without prior assumption regarding the nature of the order parameter of the transition. Results from our machine learning study provide strong support in favour of a two-states model approach of membrane fluidity.

Coarse-Grain Simulations of Solid Supported Lipid Bilayers with Varying Hydration Levels.

Supported lipid bilayers (SLBs) are a very popular system for the study of biomimetic membranes. Understanding of the interactions between the solid substrate and the lipid membrane opens pathways to the design of new materials with fine-tunable properties. While it is possible to study SLBs via molecular dynamics (MD) simulations, difficulties still remain for these strategies; in particular, the confined water layer thickness and structure are difficult to reproduce in simulations. We have explored different coarse-grained (CG) models for the membrane/support interaction, and their impact on the substrate hydration level. Our results highlight the relevance of including long-range interactions in CG-MD simulations of fluid SLBs. Modeled neutron reflectivity curves are deduced from the structures obtained by molecular simulations, and substrate parameters are optimized to match the experimental and modeled reflectivity curves. We expect our coarse-grained approach to open new perspectives for the simulations of SLBs of increasing complexity, including lipid layers of complex compositions, or adsorbed lipidic layers on patterned surfaces.

Interaction of Giant Unilamellar Vesicles with the Surface Nanostructures on Dragonfly Wings.

The waxy epicuticle of dragonfly wings contains a unique nanostructured pattern that exhibits bactericidal properties. In light of emerging concerns of antibiotic resistance, these mechano-bactericidal surfaces represent a particularly novel solution by which bacterial colonization and the formation of biofilms on biomedical devices can be prevented. Pathogenic bacterial biofilms on medical implant surfaces cause a significant number of human deaths every year. The proposed mechanism of bactericidal activity is through mechanical cell rupture; however, this is not yet well understood and has not been well characterized. In this study, we used giant unilamellar vesicles (GUVs) as a simplified cell membrane model to investigate the nature of their interaction with the surface of the wings of two dragonfly species, Austrothemis nigrescens and Trithemis annulata, sourced from Victoria, Australia, and the Baix Ebre and Terra Alta regions of Catalonia, Spain. Confocal laser scanning microscopy and cryo-scanning electron microscopy techniques were used to visualize the interactions between the GUVs and the wing surfaces. When exposed to both natural and gold-coated wing surfaces, the GUVs were adsorbed on the surface, exhibiting significant deformation, in the process of membrane rupture. Differences between the tensile rupture limit of GUVs composed of 1,2-dioleoyl- sn-glycero-3-phosphocholine and the isotropic tension generated from the internal osmotic pressure were used to indirectly determine the membrane tensions, generated by the nanostructures present on the wing surfaces. These were estimated as being in excess of 6.8 mN m-1, the first experimental estimate of such mechano-bactericidal surfaces. This simple model provides a convenient bottom-up approach toward understanding and characterizing the bactericidal properties of nanostructured surfaces.

Kinetic evolution of DOPC lipid bilayers exposed to α-cyclodextrins.

Cyclodextrins are cyclic oligosaccharides capable of forming inclusion complexes with a variety of molecules, and as such have been recognized as a pharmaceutical and biotechnological asset. Cyclodextrins are known to interact with the components of cell membranes, and this correlates with a significant degree of cytotoxicity. In this work, we report on the mechanism of degradation of a model dioleoyl-phosphatidylcholine (DOPC) bilayer exposed to a solution with increasing concentrations of α-cyclodextrins. By combining optical fluorescence microscopy and quartz-crystal microbalance experiments, we study the evolution of supported lipid bilayers (SLBs) and giant unilamellar vesicles (GUVs). The rate of lipid removal is found to display a strong nonlinear dependence on the cyclodextrin concentration. A mechanism involving lipid aggregates is proposed.

Permeability of DOPC bilayers under photoinduced oxidation: Sensitivity to photosensitizer.

The modification of lipid bilayer permeability is one of the most striking yet poorly understood physical transformations that follow photoinduced lipid oxidation. We have recently proposed that the increase of permeability of photooxidized 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) bilayers is controlled by the time required by the oxidized lipid species to diffuse and aggregate into pores. Here we further probe this mechanism by studying photosensitization of DOPC membranes by methylene blue (MB) and DO15, a more hydrophobic phenothiazinium photosensitizer, under different irradiation powers. Our results not only reveal the interplay between the production rate and the diffusion of the oxidized lipids, but highlight also the importance of photosensitizer localization in the kinetics of oxidized membrane permeability.

DPPC Bilayers in Solutions of High Sucrose Content.

The properties of lipid bilayers in sucrose solutions have been intensely scrutinized over recent decades because of the importance of sugars in the field of biopreservation. However, a consensus has not yet been formed on the mechanisms of sugar-lipid interaction. Here, we present a study on the effect of sucrose on 1,2-dipalmitoyl-sn-glycero-3-phosphocholine bilayers that combines calorimetry, spectral fluorimetry, and optical microscopy. Intriguingly, our results show a significant decrease in the transition enthalpy but only a minor shift in the transition temperature. Our observations can be quantitatively accounted for by a thermodynamic model that assumes partial delayed melting induced by sucrose adsorption at the membrane interface.

Influence of a pH-sensitive polymer on the structure of monoolein cubosomes.

Cubosomes consist in submicron size particles of lipid bicontinuous cubic phases stabilized by surfactant polymers. They provide an appealing road towards the practical use of lipid cubic phases for pharmaceutical and cosmetic applications, and efforts are currently being made to control the encapsulation and release properties of these colloidal objects. We overcome in this work the lack of sensitivity of monoolein cubosomes to pH conditions by using a pH sensitive polymer designed to strongly interact with the lipid structure at low pH. Our cryo-transmission electron microscope (cryo-TEM) and small-angle X-ray scattering (SAXS) results show that in the presence of the polymer the cubic phase structure is preserved at neutral pH, albeit with a larger cell size. At pH 5.5, in the presence of the polymer, the nanostructure of the cubosome particles is significantly altered, providing a pathway to design pH-responsive cubosomes for applications in drug delivery.

Hemodynamic forces can be accurately measured in vivo with optical tweezers.

Force sensing and generation at the tissue and cellular scale is central to many biological events. There is a growing interest in modern cell biology for methods enabling force measurements in vivo. Optical trapping allows noninvasive probing of piconewton forces and thus emerged as a promising mean for assessing biomechanics in vivo. Nevertheless, the main obstacles lie in the accurate determination of the trap stiffness in heterogeneous living organisms, at any position where the trap is used. A proper calibration of the trap stiffness is thus required for performing accurate and reliable force measurements in vivo. Here we introduce a method that overcomes these difficulties by accurately measuring hemodynamic profiles in order to calibrate the trap stiffness. Doing so, and using numerical methods to assess the accuracy of the experimental data, we measured flow profiles and drag forces imposed to trapped red blood cells of living zebrafish embryos. Using treatments enabling blood flow tuning, we demonstrated that such a method is powerful in measuring hemodynamic forces in vivo with accuracy and confidence. Altogether this study demonstrates the power of optical tweezing in measuring low range hemodynamic forces in vivo and offers an unprecedented tool in both cell and developmental biology.

Peroxidised phospholipid bilayers: insight from coarse-grained molecular dynamics simulations.

An original coarse-grained model for peroxidised phospholipids is presented, based on the MARTINI lipid force field. This model results from a combination of thermodynamic modelling and structural information on the area per lipid, which have been made available recently. The resulting coarse-grained lipid molecules form stable bilayers, and a set of elastic coefficients (compressibility and bending moduli) is obtained. We compare the compressibility coefficient to the experimental values [Weber et al., Soft Matter, 2014, 10, 4241]. Predictions for the mechanical properties, membrane thickness and lateral distribution of hydroperoxide groups in the phospholipid bilayer are presented.

Physical damage on giant vesicles membrane as a result of methylene blue photoirradiation.

In this study we pursue a closer analysis of the photodamage promoted on giant unilamellar vesicles membranes made of dioleoyl-sn-glycero-3-phosphocholine (DOPC) or 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), by irradiating methylene blue present in the giant unilamellar vesicles solution. By means of optical microscopy and electro-deformation experiments, the physical damage on the vesicle membrane was followed and the phospholipids oxidation was evaluated in terms of changes in the membrane surface area and permeability. As expected, oxidation modifies structural characteristics of the phospholipids that lead to remarkable membrane alterations. By comparing DOPC- with POPC-made membranes, we observed that the rate of pore formation and vesicle degradation as a function of methylene blue concentration follows a diffusion law in the case of DOPC and a linear variation in the case of POPC. We attributed this scenario to the nucleation process of oxidized species following a diffusion-limited growth regime for DOPC and in the case of POPC a homogeneous nucleation process. On the basis of these premises, we constructed models based on reaction-diffusion equations that fit well with the experimental data. This information shows that the outcome of the photosensitization reactions is critically dependent on the type of lipid present in the membrane.

Scraping and stapling of end-grafted DNA chains by a bioadhesive spreading vesicle to reveal chain internal friction and topological complexity.

Stained end-grafted DNA molecules about 20 µm long are scraped away and stretched out by the spreading front of a bioadhesive vesicle. Tethered biotin ligands bind the vesicle bilayer to a streptavidin substrate, stapling the DNAs into frozen confinement paths. Image analysis of the stapled DNA gives access, within optical resolution, to the local stretching values of individual DNA molecules swept by the spreading front, and provides evidence of self-entanglements.