Transiciones de fase en la membrana de esfingomielina

46 páginas.Trabajo de Máster Universitario en Simulación Molecular (2020/21). Directores: Dr. D. Luis González MacDowell ; Dr. D. Pablo Llombart González. Conocer el funcionamiento de las membranas biológicas o bicapas lipídicas es de gran interés tanto para la biología como para la físico-química, debido a la complejidad de estas estructuras, que pueden transicionar entre distintas fases como la denominada cristal líquido, ondulada o la fase liquida ordenada. Por la dificultad de poder obtener estas estructuras de una forma pura y gracias a los avances en la tecnología y los estudios de dinámica molecular, este trabajo ha tratado de simular el comportamiento de una membrana monocomponente formada por una bicapa de esfingomielina sometiéndola a temperaturas que varían entre los 0 y los 75ºC , en un sistema formado por la bicapa de estudio en un entorno de solvente agua. Las simulaciones se realizaron accediendo a los ordenadores pertenecientes a Camaragibe de la Universidad Complutense de Madrid a distancia, utilizando el paquete de software libre GROMACS y utilizando los modelos de campo de fuerza GROMOS54A7 y de agua SPC, todo ello facilitado por los doctores Pablo Llombart y Luis G. MacDowell, supervisores de este trabajo. De las simulaciones se obtuvo información relacionada con características como los perfiles de densidad, área por lípido, el desplazamiento cuadrático media o los coeficientes de difusión de la membrana, gracias a la que podemos observar las características de las distintas fases por las que pasa la membrana. La membrana pasa por estos estados conforme aumenta la temperatura, variando también su densidad, ancho, área por lípido y difusividad, afectando los cambios de temperatura al sistema y haciendo que al final la membrana pase a un estado más desordenado o fluido. Estos resultados concuerdan con lo visto en estudios previos de lípidos en sistemas parecidos.Understanding the behaviour of biological membranes or lipid bilayers is of major interest for both biology and physico-chemistry, because of to the complexity of these structures, which can transition between different phases such as liquid crystal, ripple or ordered liquid phases. Due to the difficulty of obtaining these structures in a pure form and thanks to advances in technology and molecular dynamics studies, this work has tried to simulate the behavior of a monocomponent membrane formed by a sphingomyelin bilayer by subjecting it to temperatures ranging between 0 and 75ºC, in a system formed by the bilayer of study in a water solvent environment. The simulations were performed by accessing the computers belonging to Camaragibe of the Universidad Complutense de Madrid remotely, using the free software package GROMACS and using the GROMOS54A7 force field and SPC water models, all provided by Dr. Pablo Llombart and Dr. Luis G. MacDowell, supervisors of this work. From the simulations we obtained information related to characteristics such as density profiles, area per lipid, mean square displacement or diffusion coefficients of the membrane, thanks to which we can observe the characteristics of the different phases through which the membrane passes. The membrane passes through these states as temperature increases, varying in density, width, area per lipid and diffusivity, with temperature changes affecting the system and ultimately causing the membrane to move to a more disordered or fluid state. These results are consistent with previous studies of lipids in similar systems

The Influence of Coronary Artery Disease in the Development of Aortic Stenosis and the Importance of the Albumin Redox State.

Calcific aortic valve and coronary artery diseases are related cardiovascular pathologies in which common processes lead to the calcification of the corresponding affected tissue. Among the mechanisms involved in calcification, the oxidative stress that drives the oxidation of sulfur-containing amino acids such ascysteines is of particular interest. However, there are important differences between calcific aortic valve disease and coronary artery disease, particularly in terms of the reactive oxygen substances and enzymes involved. To evaluate what effect coronary artery disease has on aortic valves, we analyzed valve tissue from patients with severe calcific aortic stenosis with and without coronary artery disease. Proteins and peptides with oxidized cysteines sites were quantified, leading to the identification of 16 proteins with different levels of expression between the two conditions studied, as well as differences in the redox state of the tissue. We also identified two specific sites of cysteine oxidation in albumin that have not been described previously. These results provide evidence that coronary artery disease affects valve calcification, modifying the molecular profile of aortic valve tissue. In addition, the redox proteome is also altered when these conditions coincide, notably affecting human serum albumin.This research was funded by the Junta de Comunidades de Castilla-La Mancha (JCCM, co-funded by the European Social Fund, SBPLY/19/180501/000226), the Instituto de Salud Carlos III through the project PI18/00995, PI21/00384 (co-funded by European Regional Development Fund/European Social Fund—“Investing in your future”) Sociedad Española de Cardiología, 2020, Grant PRB3 (IPT17/0019—ISCIII-SGEFI/ERDF), Spanish Ministry of Science, Innovation and Universities (PGC2018-097019-B-I00) and “la Caixa” Banking Foundation (project code HR17-00247). These results are aligned with the Spanish initiative on the Human Proteome Project (SpHPP).S