RESUMEN
The diagnosis of aneurysms is informed by empirically tracking their size and growth rate. Here, by analysing the growth of aortic aneurysms from first principles via linear stability analysis of flow through an elastic blood vessel, we show that abnormal aortic dilatation is associated with a transition from stable flow to unstable aortic fluttering. This transition to instability can be described by the critical threshold for a dimensionless number that depends on blood pressure, the size of the aorta, and the shear stress and stiffness of the aortic wall. By analysing data from four-dimensional flow magnetic resonance imaging for 117 patients who had undergone cardiothoracic imaging and for 100 healthy volunteers, we show that the dimensionless number is a physiomarker for the growth of thoracic ascending aortic aneurysms and that it can be used to accurately discriminate abnormal versus natural growth. Further characterization of the transition to blood-wall fluttering instability may aid the understanding of the mechanisms underlying aneurysm progression in patients.
Asunto(s)
Aneurisma de la Aorta Torácica , Humanos , Aneurisma de la Aorta Torácica/diagnóstico por imagen , Presión SanguíneaRESUMEN
Rupture of aortic aneurysms is by far the most fatal heart disease, with a mortality rate exceeding 80%. There are no reliable clinical protocols to predict growth, dissection, and rupture because the fundamental physics driving aneurysm progression is unknown. Here, via in-vitro experiments, we show that a blood-wall, fluttering instability manifests in synthetic arteries under pulsatile forcing. We establish a phase space to prove that the transition from stable flow to unstable aortic flutter is accurately predicted by a flutter instability parameter derived from first principles. Time resolved strain maps of the evolving system reveal the dynamical characteristics of aortic flutter that drive aneurysm progression. We show that low level instability can trigger permanent aortic growth, even in the absence of material remodeling. Sufficiently large flutter beyond a secondary threshold localizes strain in the walls to the length scale clinically observed in aortic dissection. Lastly, significant physical flutter beyond a tertiary threshold can ultimately induce aneurysm rupture via failure modes reported from necropsy. Resolving the fundamental physics of aneurysm progression directly leads to clinical protocols that forecast growth as well as intercept dissection and rupture by pinpointing their physical origin.
RESUMEN
Gas vesicles (GVs) are proteinaceous cylindrical shells found within bacteria or archea growing in aqueous environments and are composed primarily of two proteins, gas vesicle protein A and C (GvpA and GvpC). GVs exhibit strong performance as next-generation ultrasound contrast agents due to their gas-filled interior, tunable collapse pressure, stability in vivo and functionalizable exterior. However, the exact mechanism leading to GV collapse remains inconclusive, which leads to difficulty in predicting collapse pressures for different species of GVs and in extending favorable nonlinear response regimes. Here, we propose a two stage mechanism leading to GV loss of echogenicity and rupture under hydrostatic pressure: elastic buckling of the cylindrical shell coupled with condensation driven weakening of the GV membrane. Our goal is to therefore test whether the final fracture of the GV membrane occurs by the interplay of both mechanisms or purely through buckling failure as previously believed. To do so, we (1) compare the theoretical condensation and buckling pressures with that for experimental GV collapse and (2) describe how condensation can lead to plastic buckling failure. GV shell properties that are necessary input to this theoretical description, such as the elastic moduli and wettability of GvpA, are determined using molecular dynamics simulations of a novel structural model of GvpA that better represents the hydrophobic core. For GVs that are not reinforced by GvpC, this analytical framework shows that the experimentally observed pressures resulting in loss of echogenicity coincide with both the elastic buckling and condensation pressure regimes. We also found that the stress strain curve for GvpA wetted on both the interior and exterior exhibits a loss of mechanical stability compared to GvpA only wetted on the exterior by the bulk solution. We identify a pressure vs. vesicle size regime where condensation can occur prior to buckling, which may preclude nonlinear shell buckling responses in contrast imaging.
RESUMEN
The coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains an extant threat against public health on a global scale. Cell infection begins when the spike protein of SARS-CoV-2 binds with the human cell receptor, angiotensin-converting enzyme 2 (ACE2). Here, we address the role of tetracycline as an inhibitor for the receptor-binding domain (RBD) of the spike protein. Targeted molecular investigation show that tetracycline binds more favorably to the RBD (-9.40 kcal/mol) compared to doxycycline (-8.08 kcal/mol), chloroquine (-6.31 kcal/mol), or gentamicin (-4.83 kcal/mol) while inhibiting attachment to ACE2 to a greater degree (binding efficiency of 2.98 kcal/(mol nm2 ) for tetracycline-RBD, 5.16 kcal/(mol nm2 ) for doxycycline-RBD, 5.59 kcal/(mol nm2 ) for chloroquine-RBD, and 7.02 kcal/(mol nm2 ) for gentamicin-RBD. Stronger inhibition by tetracycline is verified with nonequilibrium PMF calculations, for which the tetracycline-RBD complex exhibits the lowest free energy profile along the dissociation pathway from ACE2. Tetracycline binds to tyrosine and glycine residues on the viral contact interface that are known to modulate molecular recognition and bonding affinity. These RBD residues also engage in significant hydrogen bonding with the human receptor ACE2. The ability to preclude cell infection complements the anti-inflammatory and cytokine suppressing capability of tetracycline; this may reduce the duration of ICU stays and mechanical ventilation induced by the coronavirus SARS-CoV-2.
Asunto(s)
Enzima Convertidora de Angiotensina 2/antagonistas & inhibidores , Antivirales/farmacología , Tratamiento Farmacológico de COVID-19 , Receptores Virales/antagonistas & inhibidores , Tetraciclina/farmacología , COVID-19/patología , Cloroquina/farmacología , Doxiciclina/farmacología , Gentamicinas/farmacología , Humanos , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Unión Proteica/efectos de los fármacos , Dominios Proteicos , SARS-CoV-2/efectos de los fármacos , Glicoproteína de la Espiga del Coronavirus/metabolismoRESUMEN
Above a critical temperature known as the Leidenfrost point (LFP), a heated surface can suspend a liquid droplet above a film of its own vapor. The insulating vapor film can be highly detrimental in metallurgical quenching and thermal control of electronic devices, but may also be harnessed to reduce drag and generate power. Manipulation of the LFP has occurred mostly through experiment, giving rise to a variety of semiempirical models that account for the Rayleigh-Taylor instability, nucleation rates, and superheat limits. However, formulating a truly comprehensive model has been difficult given that the LFP varies dramatically for different fluids and is affected by system pressure, surface roughness, and liquid wettability. Here, we investigate the vapor film instability for small length scales that ultimately sets the collapse condition at the Leidenfrost point. From a linear stability analysis, it is shown that the main film-stabilizing mechanisms are the liquid-vapor surface tension-driven transport of vapor mass and the evaporation at the liquid-vapor interface. Meanwhile, van der Waals interaction between the bulk liquid and the solid substrate across the vapor phase drives film collapse. This physical insight into vapor film dynamics allows us to derive an ab initio, mathematical expression for the Leidenfrost point of a fluid. The expression captures the experimental data on the LFP for different fluids under various surface wettabilities and ambient pressures. For fluids that wet the surface (small intrinsic contact angle), the expression can be simplified to a single, dimensionless number that encapsulates the wetting instability governing the LFP.
RESUMEN
Numerous studies have focused on designing functional surfaces that delay frost formation or reduce ice adhesion. However, solutions to the scientific challenges of developing antiicing surfaces remain elusive because of degradation such as mechanical wearing. Inspired by the discontinuous frost pattern on natural leaves, here we report findings on the condensation frosting process on surfaces with serrated structures on the millimeter scale, which is distinct from that on a conventional planar surface with microscale/nanoscale textures. Dropwise condensation, during the first stage of frosting, is enhanced on the peaks and suppressed in the valleys, causing frost to initiate from the peaks, regardless of surface chemistry. The condensed droplets in the valley are then evaporated due to the lower vapor pressure of ice compared with water, resulting in a frost-free zone in the valley, which resists frost propagation even on superhydrophilic surfaces. The dependence of the frost-free areal fraction on the geometric parameters and the ambient conditions is elucidated by both numerical simulations based on steady-state diffusion and an analytical method with an understanding of boundary conditions independent of surface chemistry. We envision that this study would provide a unified framework to design surfaces that can spatially control frost formation, crystal growth, diffusion-controlled growth of biominerals, and material deposition over a broad range of applications.
RESUMEN
The Leidenfrost layer is characterized by an insulating vapor film between a heated surface and an ambient liquid. The collapse of this film has been canonically theorized to occur from an interfacial instability between the liquid and vapor phases. The interfacial instability alone, however, is insufficient to explain the known influence of the surface on the film collapse process. In this work, we provide visual evidence for two key mechanisms governing the film collapse: the interfacial instability, and the nucleation of vapor upon multiple non-terminal liquid-solid contacts. These results were obtained by implementing high-speed X-ray imaging of the film collapse on a heated sphere submerged in liquid-water. The X-ray images were synchronized with a second high-speed visible light camera and two thermocouples to provide insight into the film formation and film collapse processes. Lastly, the dynamic film thickness was quantified by analysis of the X-ray images. This helped assess the influence of surface roughness on the disruption of the film. The results of this work encourage further investigation into non-linear stability theory to consolidate the role of the surface on the liquid-vapor interface during the film collapse process.
RESUMEN
The build-up of ice on aircraft, bridges, oil rigs, wind turbines, electrical lines, and other surfaces exposed to cold environments diminishes their safe and effective operation. To engineer robust surfaces that reduce ice adhesion, it is necessary to understand the physics of what makes a surface icephobic ("ice-hating") as well as the relationship between icephobicity and ice adhesion. Here we elucidate the molecular origin of icephobicity based on ice-surface interactions and characterize the correlation between material icephobicity and liquid wettability. This fundamental understanding of icephobic characteristics enables us to propose a robust design for topologically textured, icephobic surfaces. The design identifies the critical confinement length scale to sustain liquid water (as opposed to ice) in between roughness features and can reduce the strength of ice adhesion by over a factor of twenty-seven compared to traditional hydrophobic surfaces. The reduction in ice adhesion is due to the metastability of liquid water; as ambient ice cleaves from the textured surface, liquid water leaves confinement and freezes - a process which takes the system from a local energy minimum to a global energy minimum. This phase transition generates a detachment force that actively propels ambient ice from the surface.