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Computer simulation of nanoparticles translocation through phospholipid membranes within single chain mean field approachPogodin, Sergey 11 April 2012 (has links)
Las células biológicas, bloques elementales de construcción de la materia viva,
son presentadas en grandes cantidades en nuestro planeta, y son
extremadamente importantes para nosotros, porque todos estamos hechos de
ellos. Un componente esencial de cada célula es la membrana celular,
protegiendo las células del medio ambiente y también controlando el transporte
de los productos químicos entre el interior y el exterior de la célula. Cuando un
extraño nano-objeto se aproxima a la membrana celular, las preguntas
importantes sobre su destino surgirán de manera natural. ¿Será el nano-objeto
capaz de atravesar la membrana, o la membrana lo parará? ¿Si la nano-objeto
dañará seriamente los mecanismos de membrana, provocando el muerte de la
célula, o no? Alguien puede imaginar numerosas aplicaciones prácticas de las
interacciones específicas posibles entre un nano-objeto y la membrana.
Pueden ser utilizadas, por ejemplo, para entregar una medicina necesaria
dentro de una célula enferma, o para eliminar las células dañinas específicas
por la destrucción de sus membranas o por la supresión de su correcto
funcionamiento.
Las preguntas mencionadas anteriormente son difíciles de responder en la
actualidad, tanto por los métodos experimentales como por los métodos
teóricos. La mayor dificultad es la compleja estructura de la membrana celular,
que consiste de una bicapa lipídica, con numerosas proteínas integradas en él
y ancladas a ella. La base de lípidos de la membrana está formada por una
mezcla de fosfolípidos, glucolípidos, colesterol, y los fosfolípidos son el
principal compuesto de la bicapa. Así, una bicapa de fosfolípidos puros puede
ser considerada como un modelo de una membrana de la célula real, tanto en
estudios experimentales como en unos teóricos. Se puede utilizar para estimar
las propiedades mecánicas de la membrana biológica, su permeabilidad para
diferentes productos químicos y nano-objetos, para estudiar su interacción con
las proteínas individuales.
El número de los métodos experimentales se aplican con éxito para / Biological cells, elementary building blocks of the live matter, are presented in
large amounts on our planet, and they are extremely important for us, because
all we are made of them. An essential component of every cell is the cell
membrane, protecting the cell from the environment and also controlling the
transport of chemicals between the interior and exterior of the cell. When an
extraneous nano-object approaches the cell membrane, important questions
about their destiny arise naturally. Will be the nano-object able to pass through
the membrane, or will the membrane stop it? Will the nano-object severely
damage the membrane machinery, causing the cell death, or not? One can
image numerous practical applications of specific interactions possible between
a nano-object and the membrane. They may be used, for example, to deliver a
necessary medicine inside a deceased cell, or to kill some specific harmful cells
by destruction of their membranes or by suppression of their proper functioning.
The questions outlined above are hard to answer at the present day, both using
experimental or theoretical methods. The major difficulty is the complex
structure of the cell membrane, consisting of lipid bilayer, with numerous
proteins embed into it and anchored to it. The lipid basement of the membrane
is formed by mixture of phospholipids, glycolipids, cholesterol, and the
phospholipids are the major compound of the bilayer. Thus a pure phospholipid
bilayer can be considered as a model of a real cell membrane both in
experimental and theoretical studies. It can be used to estimate mechanical
properties of the biological membrane, its permeability for different chemicals
and nano-objects, to study its interaction with single proteins.
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SOLID-STATE NMR SPECTROSCOPIC STUDIES OF PROTEINS AND SMALL MOLECULES IN PHOSPHOLIPID MEMBRANESChu, Shidong 06 August 2010 (has links)
No description available.
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Water-Soluble Deep-Cavity Cavitands: Synthesis, Molecular Recognition, and Interactions with Phospholipid MembranesIoup, Sarah E 15 December 2012 (has links)
Water-soluble deep-cavity cavitands provide a rare opportunity to study self-assembly driven by the hydrophobic effect. These molecular hosts dimerize in the presence of certain guest molecules to form water-soluble molecular capsules. These systems have given rise to numerous novel chemical phenomena and have potential use in drug delivery. The host octaacid (OA) has been particularly well-characterized, but studies are limited to basic pH because of limited host solubility.
Herein we report an improved synthesis of OA and the syntheses of three new water-soluble deep-cavity cavitands. The new hosts are soluble at neutral pH, increasing relevance for biological studies. The new syntheses are versatile enough to apply to the synthesis of additional water- soluble cavitands in the future. We also describe preliminary characterization of the molecular recognition properties of the new hosts. Binding of organic guest molecules to form 1:1 host:guest complexes and 2:1 host:guest capsules was qualitatively similar to that of OA. However, binding of anions spanning the Hofmeister series revealed interesting new behavior. The new hosts bound a wider range of anions inside the hydrophobic pocket with much higher association constants. Moreover, external binding of several anions to the cavitand pendant feet was observed.
Looking towards biological applications, we desired to learn how these molecules interact with phospholipid membranes. Six water-soluble cavitands were tested for their ability to permeabilize liposomal POPC membranes. One host showed very high potency in permeabilizing membranes, while three other hosts showed moderate activity. Host binding of POPC was found to be at least one factor in host-induced permeabilization. A requenching assay to determine leakage mechanism strongly supported all-or-none leakage, whereby some vesicles lose all contents while others lose none. These results suggest that these cavitands induce partial transient leakage of vesicles by the formation of transient membrane pores. These findings show potential for the use of these hosts as drug delivery carriers, antimicrobial compounds, and tools in membrane alteration studies.
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Nuclear magnetic resonance probes of membrane biophysics: Structure and dynamicsLeftin, Avigdor January 2010 (has links)
The phospholipid membrane is a self-assembled, dynamic molecular system that may exist alone in association with only water, or in complex systems comprised of multiple lipid types and proteins. In this dissertation the intra- and inter-molecular forces responsible for the atomistic, molecular and collective equilibrium structure and dynamics are studied by nuclear magnetic resonance spectroscopy (NMR). The multinuclear NMR measurements and various experimental techniques are able to provide data that enable the characterization of the hierarchical spatio-temporal organization of the phospholipid membrane. The experimental and theoretical studies conducted target membrane interactions ranging from model systems composed of only water and lipids, to multiple component domain forming membranes that are in association with peripheral and trans-membrane proteins. These measurements consisit of frequency spectrum lineshapes and nuclear-spin relaxation rates obtained using 2 H NMR, 13 C NMR, 31 P NMR and 1 H NMR. The changes of these experimental observables are interpreted within a statistical thermodynamic framework that allows the membrane structure, activation energies, and correlation times of motion to be determined. The cases presented demonstrate how fundamental principles of NMR spectroscopy may be applied to a host of membranes, leading to the biophysical characterization of membrane structure and dynamics.
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Pokročilé membránové systémy / Advanced membrane systemsGjevik, Alžběta January 2017 (has links)
The diploma thesis deals with cellular membrane model preparation on microfluidic devices. It summarizes means of microfluidic device fabrication, phospholipid bilayer formation mechanisms, optimization techniques and characterization methods of those systems. It focuses on free-standing planar lipid bilayers which are easily accessible by a number of different characterization methods and at the same time exhibit good stability and variability. The aim of this work is to design and prepare a microfluidic chip on which a planar lipid bilayer can be prepared. It therefore presents microfluidic device prepared by soft lithography of PDMS adapted for model membrane formation by self-assembly of phospholipids at the interface of aqueous and organic phases created by the architecture of the microfluidic device. Formation of the model membrane was visualized by optical microscopy and fluorescence-lifetime imaging microscopy.
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