Faculty Bibliography

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.

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.

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.

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.

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.