On Fusogenicity of Positively Charged Phased-Separated Lipid Vesicles: Experiments and Computational Simulations.

This paper studies the fusogenicity of cationic liposomes in relation to their surface distribution of cationic lipids and utilizes membrane phase separation to control this surface distribution. It is found that concentrating the cationic lipids into small surface patches on liposomes, through phase-separation, can enhance liposome's fusogenicity. Further concentrating these lipids into smaller patches on the surface of liposomes led to an increased level of fusogenicity. These experimental findings are supported by numerical simulations using a mathematical model for phase-separated charged liposomes. Findings of this study may be used for design and development of highly fusogenic liposomes with minimal level of toxicity.

A microscopic approach to study the onset of a highly infectious disease spreading.

We combine a pedestrian dynamics model with a contact tracking method to simulate the initial spreading of a highly infectious airborne disease in a confined environment. We focus on a medium size population (up to 1000 people) with a small number of infectious people (1 or 2) and the rest of the people are divided between immune and susceptible. We adopt a space-continuous model that represents pedestrian dynamics by the forces acting on them, i.e. a microscopic force-based model. Once discretized, the model results in a high-dimensional system of second order ordinary differential equations. Before adding the contact tracking to the pedestrian dynamics model, we calibrate the model parameters, compare the model results against empirical data, and show that pedestrian self-organization into lanes can be captured. We consider an explicit approach for contact tracking by introducing a sickness domain around a sick person. A healthy but susceptible person who remains in the sickness domain for a certain amount of time may get infected (with a prescribed probability) and become a so-called secondary contact. As a concrete setting to simulate the onset of disease spreading, we consider terminals in two US airports: Hobby Airport in Houston and the Atlanta International Airport. We consider different scenarios and we quantify the increase in average number of secondary contacts as a given terminal becomes more densely populated, the percentage of immune people decreases, the number of primary contacts increases, and areas of high density (such as the boarding buses) are present.

A computational study of lateral phase separation in biological membranes.

Conservative and non-conservative phase-field models are considered for the numerical simulation of lateral phase separation and coarsening in biological membranes. An unfitted finite element method is proposed to allow for a flexible treatment of complex shapes in the absence of an explicit surface parametrization. For a set of biologically relevant shapes and parameter values, the paper compares the dynamic coarsening produced by conservative and non-conservative numerical models, its dependence on certain geometric characteristics and convergence to the final equilibrium.

3D Experimental and Computational Analysis of Eccentric Mitral Regurgitant Jets in a Mock Imaging Heart Chamber.

Mitral valve regurgitation (MR) is a disorder of the heart in which the mitral valve does not close properly. This causes an abnormal leaking of blood backwards from the left ventricle into the left atrium during the systolic contractions of the left ventricle. Noninvasive assessment of MR using echocardiography is an ongoing challenge. In particular, a major problem are eccentric or Coanda regurgitant jets which hug the walls of the left atrium and appear smaller in the color Doppler image of regurgitant flow. This manuscript presents a comprehensive investigation of Coanda regurgitant jets and the associated intracardiac flows by using a combination of experimental and computational approaches. An anatomically correct mock heart chamber connected to a pulsatile flow loop is used to generate the physiologically relevant flow conditions, and the influence of two clinically relevant parameters (orifice aspect ratio and regurgitant volume) on the onset of Coanda effect is studied. A two parameter bifurcation diagram showing transition to Coanda jets is obtained, indicating that: (1) strong wall hugging jets occur in long and narrow orifices with moderate to large regurgitant volumes, and (2) short orifices with moderate to large regurgitant volumes produce strong 3D flow features such as vortex rolls, giving rise to the velocities that are orthogonal to the 2D plane associated with the apical color Doppler views, making them "invisible" to the single plane color Doppler assessment of MR. This is the first work in which the presence of vortex rolls in the left atrium during regurgitation is reported and identified as one of the reasons for under-estimation of regurgitant volume. The results of this work can be used for better design of imaging strategies in noninvasive assessment of MR, and for better understanding of LA remodeling that may be associated with the presence of maladapted vortex dynamics. This introduces a new concept in clinical imaging, which emphasizes that the quality and not only the quantity of regurgitant flow matters in the assessment of severity of mitral valve regurgitation.

Numerical characterization of hemodynamics conditions near aortic valve after implantation of Left Ventricular Assist Device.

Left Ventricular Assist Devices (LVADs) are implantable mechanical pumps that temporarily aid the function of the left ventricle. The use of LVADs has been associated with thrombus formation next to the aortic valve and close to the anastomosis region, especially in patients in which the native cardiac function is negligible and the aortic valve remains closed. Stagnation points and recirculation zones have been implicated as the main fluid dynamics factors contributing to thrombus formation. The purpose of the present study was to develop and use computer simulations based on a fluid-structure interaction (FSI) solver to study flow conditions corresponding to different strategies in LVAD ascending aortic anastomosis providing a scenario with the lowest likelihood of thrombus formation. A novel FSI algorithm was developed to deal with the presence of multiple structures corresponding to different elastic properties of the native aorta and of the LVAD cannula. A sensitivity analysis of different variables was performed to assess their impact of flow conditions potentially leading to thrombus formation. It was found that the location of the anastomosis closest to the aortic valve (within 4 cm away from the valve) and at the angle of 30 minimizes the likelihood of thrombus formation. Furthermore, it was shown that the rigidity of the dacron anastomosis cannula plays almost no role in generating pathological conditions downstream from the anastomosis. Additionally, the flow analysis presented in this manuscript indicates that compliance of the cardiovascular tissue acts as a natural inhibitor of pathological flow conditions conducive to thrombus formation and should not be neglected in computer simulations.