Changes in free energy barrier for water permeation by stretch-induced phase transitions in phospholipid/cholesterol bilayers.

Water permeation through phospholipid/cholesterol bilayers is the key to understanding tension-induced rupture of biological cell membranes. We performed molecular dynamics simulations of stretched phospholipid/cholesterol bilayers to investigate changes in the free energy profile of water molecules across the bilayer and the lipid structure responsible for water permeation. We modeled stretching of the bilayer by applying areal strain. In stretched phospholipid/cholesterol bilayers, the hydrophobic tail of the phospholipids became disordered and the free energy barrier to water permeation decreased. Upon exceeding the critical areal strain, a phase transition to an interdigitated gel phase occurred before rupture, and the hydrophobic tail ordering as well as the free energy barrier were restored. In pure phospholipid bilayers, we did not observe such recoveries. These transient recoveries in the phospholipid/cholesterol bilayer suppressed water permeation and membrane rupture, followed by an increase in the critical areal strain at which the bilayer ruptured. This result agrees with experimental results and provides a reasonable molecular mechanism for the toughness of phospholipid/cholesterol bilayers under tension.Communicated by Ramaswamy H. Sarma.

Shear-flow-induced negative tension of phospholipid bilayer: Molecular dynamics simulation.

Shear flow has been theoretically predicted to suppress the undulation of surfactant bilayers and generate negative tension, which is considered to be a driving force of the transition from the lamellar phase to the multilamellar vesicle phase in surfactant/water suspensions, the so-called onion transition. We performed coarse-grained molecular dynamics simulations of a single phospholipid bilayer under shear flow to clarify the relationship between the shear rate, bilayer undulation, and negative tension, providing molecular-level insight into the undulation suppression. An increasing shear rate suppressed bilayer undulation and increased negative tension; these results are consistent with theoretical predictions. The non-bonded forces between the hydrophobic tails facilitated negative tension, whereas the bonded forces within the tails suppressed it. The force components of the negative tension were anisotropic in the bilayer plane and prominently changed in the flow direction, although the resultant tension was isotropic. Our findings regarding a single bilayer will underlie further simulation studies of multilamellar bilayers, including inter-bilayer interactions and topological changes of bilayers under shear flow, which are essential for the onion transition and are unresolved in the theoretical and experimental studies.

Physician eye contact in telemedicine video consultations: A cross-cultural experiment.

INTRODUCTION: Eye contact is generally considered a beneficial non-verbal behavior in patient-physician communication. Physicians are advised to simulate eye contact during video consultations by gazing at the camera, although we lack evidence that doing so is beneficial. This work is a cross-cultural experiment that aims to answer: "Are physicians who gaze at the camera during video consultations perceived as making eye contact, and are their communication skills rated higher?" METHODS: 43 Japanese and 61 Lebanese participants watched videos of physicians providing the same video consultations while gazing at the camera and screen. After watching each video, they rated the physicians' communication skills using six items from the GCRS and the MAAS-G scales. They also picked and justified their preferred physician gaze direction. RESULTS: When physicians gazed at the camera, they were perceived as making more eye contact and received higher communication and interpersonal skills ratings, both in Japan and Lebanon. The effect of gazing at the camera was consistently positive but varied by country and consultation content. In Japan, simulating eye contact improved the ratings of the attentive and caring physician, whereas in Lebanon, it improved the ratings of the tired and inattentive physician. When asked to choose their preferred gaze direction, 88.4% of Japanese and 90.2% of Lebanese participants chose camera gaze over screen gaze due to its positive effect on patient feelings and physician perception. Participants who chose screen gaze noted the unnaturalness of gazing at the camera and its potential negative impact on care quality. CONCLUSION: Physicians providing video consultations can simulate eye contact by gazing at the camera. Doing so improves their communication and interpersonal skills ratings and could potentially enhance their communication with their patients. Mainstream video conferencing platforms could implement gaze correction methods to simulate eye contact without affecting the physicians' experience and capacity to provide quality care.

Development of a mesoscopic framework spanning nanoscale protofibril dynamics to macro-scale fibrin clot formation.

Thrombi form a micro-scale fibrin network consisting of an interlinked structure of nanoscale protofibrils, resulting in haemostasis. It is theorized that the mechanical effect of the fibrin clot is caused by the polymeric protofibrils between crosslinks, or to their dynamics on a nanoscale order. Despite a number of studies, however, it is still unknown, how the nanoscale protofibril dynamics affect the formation of the macro-scale fibrin clot and thus its mechanical properties. A mesoscopic framework would be useful to tackle this multi-scale problem, but it has not yet been established. We thus propose a minimal mesoscopic model for protofibrils based on Brownian dynamics, and performed numerical simulations of protofibril aggregation. We also performed stretch tests of polymeric protofibrils to quantify the elasticity of fibrin clots. Our model results successfully captured the conformational properties of aggregated protofibrils, e.g., strain-hardening response. Furthermore, the results suggest that the bending stiffness of individual protofibrils increases to resist extension.

Assessment of long-range cross-correlations in cardiorespiratory and cardiovascular interactions.

We propose higher-order detrending moving-average cross-correlation analysis (DMCA) to assess the long-range cross-correlations in cardiorespiratory and cardiovascular interactions. Although the original (zeroth-order) DMCA employs a simple moving-average detrending filter to remove non-stationary trends embedded in the observed time series, our approach incorporates a Savitzky-Golay filter as a higher-order detrending method. Because the non-stationary trends can adversely affect the long-range correlation assessment, the higher-order detrending serves to improve accuracy. To achieve a more reliable characterization of the long-range cross-correlations, we demonstrate the importance of the following steps: correcting the time scale, confirming the consistency of different order DMCAs, and estimating the time lag between time series. We applied this methodological framework to cardiorespiratory and cardiovascular time series analysis. In the cardiorespiratory interaction, respiratory and heart rate variability (HRV) showed long-range auto-correlations; however, no factor was shared between them. In the cardiovascular interaction, beat-to-beat systolic blood pressure and HRV showed long-range auto-correlations and shared a common long-range, cross-correlated factor. This article is part of the theme issue 'Advanced computation in cardiovascular physiology: new challenges and opportunities'.

A braided stent becomes flattened inside a curved catheter tube: A micro-CT imaging study.

BACKGROUND: The braided stent is a widely accepted endovascular treatment device consisting of woven metal wires. One of the unsolved issues for the braided stent is the stent flattening phenomena when deployed into highly curved arteries. Although a recent computational study highlighted that the mechanical state of the stent inside the catheter before the deployment plays an essential role in causing stent flattening, there is no experimental observation for the stent inside the curved catheter. OBJECTIVE: We investigated braided stent shapes in curved catheter tubes with various curvatures by micro-computed tomography (CT). METHODS: A braided stent was deployed into catheter tubes and set in rectangular cases with constant curvature. The three-dimensional shape of the stent was imaged by micro-CT, and its cross-sectional flatness was quantitatively assessed. RESULTS: Stent flattening occurred in cases of high curvatures of the outer side of the tube curvature, and the degree of flatness increased with increasing tube curvature. This demonstrates that stent flattening can be caused inside the highly curved catheter before deployment. CONCLUSIONS: This preliminary and first observational report provides new insight into the mechanism of stent flattening and emphasizes the importance of the geometrical and mechanical state of the stent inside the catheter.

Kelvin-Helmholtz-like instability of phospholipid bilayers under shear flow: System-size dependence.

We performed a series of molecular dynamics (MD) simulations of phospholipid bilayers under shear flow to estimate the effect of the system size on Kelvin-Helmholtz (KH)-like instability of the bilayer at the molecular scale. To extend the estimation by the MD simulations to the microscale, we introduced linear stability analysis for the fluid-fluid interface consisting of a thin membrane. For both the MD simulations and theoretical model, the critical velocity difference across the bilayer, where instability occurs, decreased with increasing wavelength of the bilayer undulation λ, which corresponds to the system size. When λ was more than about ten times larger than the bilayer thickness, the critical velocity difference in the MD simulations was in quantitative agreement with that obtained by the theoretical model. This means that the theoretical model is applicable for the shear-induced KH-like instability of the bilayer for large λ. The theoretical model showed that the critical velocity difference for the KH-like instability was proportional to λ^{-3/2}. Based on these results, we discuss the implications of the shear-induced bilayer instability in the shear-induced cell damage observed in experiments.

Bicelle-to-Vesicle Transition of a Binary Phospholipid Mixture Guided by Controlled Local Lipid Compositions: A Molecular Dynamics Simulation Study.

An essential step of nanoliposome formation in an aqueous lipid solution is the transition from discoidal lipid aggregate (bicelle) to vesicle. We investigate here the bicelle-to-vesicle transition of a binary lipid mixture of saturated and unsaturated phosphatidylcholine by performing nonequilibrium molecular dynamics simulations with the coarse-grained representation of di-palmitoyl-phosphatidyl-choline (DPPC) and di-linoleoyl-phosphatidyl-choline (DLiPC). When the DPPC molecules of a stable DPPC bicelle are randomly replaced with the DLiPC molecules, the transition occurs for higher apparent DLiPC concentrations. On the other hand, when the DPPC molecules only in the core region of the bicelle are replaced, the transition occurs even for lower apparent DLiPC concentrations. For the bicelle where the head and tail layers are pure DPPC and DLiPC monolayers, respectively, the side of the DLiPC monolayer becomes the concave surface of bending bicelle. Controlling the local lipid compositions in a binary lipid bicelle has the potential to determine the success of vesicle formation and the direction of bicelle bending. Our findings help explain nanoliposome formation with sonication and give useful information for controlling encapsulation efficiencies of nanoliposomes.

Stretch-Induced Interdigitation of a Phospholipid/Cholesterol Bilayer.

The interdigitated gel (LßI) phase is one of the membrane phases of phospholipid molecules in which the hydrophobic tails of the phospholipid molecules penetrate the opposite leaflet of the bilayer. Recent molecular dynamics (MD) simulations have shown that interdigitation can take place as a phase transition from the liquid-ordered (Lo) phase to the LßI phase under stretching. However, there is still no conclusive experimental evidence for this process, so its existence remains controversial. In this study, to explain the transition from energy balance, we propose a free-energy model. The model consists of three energy components: the elastic deformation energy, surface energy at the bilayer-water interface, and interphase boundary energy. To determine the parameters of the model, we perform MD simulations of a stretched 1,2-dipalmitoyl- sn-glycero-3-phosphocholine/cholesterol bilayer. The phase diagrams from our model are in good agreement with those obtained from MD simulations. The energy balance among the components in the stretched bilayer quantitatively explains the stretch-induced transition. In the model, increasing the system size to that used in experiments shows that interdigitation is favorable for rigid bilayers under stretching or in alcohol solutions. These results suggest that the stretch-induced interdigitation might be observed in microscopic experiments.

Effects of Stretching Speed on Mechanical Rupture of Phospholipid/Cholesterol Bilayers: Molecular Dynamics Simulation.

Rupture of biological cell membrane under mechanical stresses is critical for cell viability. It is triggered by local rearrangements of membrane molecules. We investigated the effects of stretching speed on mechanical rupture of phospholipid/cholesterol bilayers using unsteady molecular dynamics simulations. We focused on pore formation, the trigger of rupture, in a 40 mol% cholesterol-including bilayer. The unsteady stretching was modeled by proportional and temporal scaling of atom positions at stretching speeds from 0.025 to 30 m/s. The effects of the stretching speed on the critical areal strain, where the pore forms, is composed of two regimes. At low speeds (<1.0 m/s), the critical areal strain is insensitive to speed, whereas it significantly increases at higher speeds. Also, the strain is larger than that of a pure bilayer, regardless of the stretching speeds, which qualitatively agrees with available experimental data. Transient recovery of the cholesterol and phospholipid molecular orientations was evident at lower speeds, suggesting the formation of a stretch-induced interdigitated gel-like phase. However, this recovery was not confirmed at higher speeds or for the pure bilayer. The different responses of the molecular orientations may help explain the two regimes for the effect of stretching speed on pore formation.

Molecular dynamics simulations of pore formation in stretched phospholipid/cholesterol bilayers.

Molecular dynamics (MD) simulations of pore formation in stretched dipalmitoylphosphatidylcholine (DPPC) bilayers containing different concentrations of cholesterol (0, 20, 40, and 60 mol%) are presented. The stretched bilayers were simulated by constant NPZA||T MD simulations with various constant areas. The effects of the cholesterol concentration on pore formation are examined in terms of the critical areal strain where the pore is formed, the processes of pore formation, and the change in molecular orientation of the DPPC molecules by analyzing the order parameters and radial distribution functions of the DPPC molecules. With increasing cholesterol concentration, the critical areal strain initially increases, peaks at 40 mol%, and then decreases, which agrees well with the available experimental data. For the bilayers containing cholesterol, DPPC molecules become disordered at low areal strains, whereas the order slightly increases when the areal strain exceeds a certain value depending on the cholesterol concentration. For 40 mol% cholesterol, the two monolayers in the bilayer interpenetrate under high areal strains, inducing an increase of the order parameters and the peak positions of the radial distribution function compared with their states at low areal strains, indicating the formation of an interdigitated gel-phase-like structure. The transient increasing of the order of the molecular orientations may inhibit water penetration into the bilayer, resulting in increased critical areal strain in the phospholipid/cholesterol bilayers.