Current Topics in Membranes is targeted toward scientists and researchers in biochemistry and molecular and cellular biology, providing the necessary membrane research to assist them in discovering the current state of a particular field and in learning where that field is heading. This volume offers an up to date presentation of current knowledge in the field of Lipid Domains. Written by leading experts Contains original material, both textual and illustrative, that should become a very relevant reference material The material is presented in a very comprehensive manner Both researchers in the field and general readers should find relevant and up-to-date information
The interface between a living cell and the surrounding world plays a critical role in numerous complex biological processes. Sperm/egg fusion, virus/cell fusion, exocytosis, endocytosis, and ion permeation are a few examples of processes involving membranes. In recent years, powerful tools such as X-ray crystal lography, electron microscopy, nuclear magnetic resonance, and infra-red and Raman spectroscopy have been developed to characterize the structure and dy namics of biomembranes. Despite this progress, many of the factors responsible for the function of biomembranes are still not well understood. The membrane is a very complicated supramolecular liquid-crystalline structure that is largely composed of lipids, forming a bilayer, to which proteins and other biomolecules are anchored. Often, the lipid bilayer environment is pictured as a hydropho bic structureless slab providing a thermodynamic driving force to partition the amino acids of a membrane protein according to their solubility. However, much of the molecular complexity of the phospholipid bilayer environment is ignored in such a simplified view. It is likely that the atomic details of the polar head group region and the transition from the bulk water to the hydrophobic core of the membrane are important. An understanding of the factors responsible for the function of biomembranes thus requires a better characterization at the molec ular level of how proteins interact with lipid molecules, of how lipids affect protein structure and of how lipid molecules might regulate protein function.
Cellular membranes are made up of phospholipids, proteins and cholesterol. The packing of components within the membrane gives rise to important biological phenomena. Understanding these interactions is the most critical step towards predicting membrane behavior. In this dissertation, I focus on lipid bilayer interactions with various molecules. At biologically relevant scale, we investigate how phospholipids interact with small molecules like amino acid residues and cholesterol. At field scale, we study the structure and dynamics of lipid molecules as they bind with clay minerals. I utilize molecular dynamics simulation, both equilibrium and biased, at both coarse-grained and atomistic level to study how these interactions impact membrane thermodynamic properties. I first study membrane permeation by evaluating the efficiency of different computational methods to sample the configurational space of various amino acid and lipid membranes. I show that replica exchange umbrella sampling out-performs others because of the algorithm's ability to sample transition state. Using this method, I calculate cholesterol chemical potential in seven binary lipid membranes. These results demonstrate the sensitivity of the cholesterol chemical potential to the lipid tail unsaturation only if the difference in tail saturation is big, and show that cholesterol has the greatest affinity to saturated PC lipids. These studies provide practical guidance for studying membrane permeation and yield important insight into the thermodynamic properties of lipid bilayer systems. This work will also contribute towards the understanding of cholesterol's effect of membranes, which is a vast and still ongoing field of research. Finally, this research also sheds lights on soil water repellency at the molecular scale. I investigate structural properties of organic matter that are found in soil and find that zwitterionic lipid aggregates bind to the surface of the clay. In this relatively new field, such molecular simulations will have significant scientific impact.
The lipid bilayer is central to life, as all living organisms possess a lipid bilayer structure, thereby underlying the lipid bilayer principle of biomembranes. The lipid bilayer principle and its applications are the main theme of this new book series. This new series on bilayer lipid membranes (BLMs and liposomes) include invited chapters on a broad range of topics, from theoretical investigations, specific studies, experimental methods, to practical applications. Written for newcomers, experienced scientists, and those who are not familiar with these specific research areas, the Series covers all aspects of lipid bilayer investigations, both fundamental and applied. * Covers a broad range of topics ranging from theoretical research, specific studies, experimental methods, to practical applications * Authoritative timely reviews by experts in this field * Indispensable source of information for new scientists
The plasma membrane defines a eukaryotic cell, separating the cell's interior from its surroundings. Structurally, the plasma membrane is a lipid bilayer, composed of numerous different lipids and proteins. A biophysical approach to understanding this system examines the behavior of the liquid crystal phases of the membrane's lipids. In particular, membrane rafts, regions with distinct physical properties, may be studied in model membranes using coexisting liquid phases containing as few as three lipid components. The findings described in this dissertation employ Molecular Dynamics simulations, computational models of the physics of interacting atoms and molecules, to explore the biophysical chemistry of lipid bilayers. Coarse-grained Molecular Dynamics simulations use simplified molecular models, which makes reproducing spontaneous demixing into coexisting liquid phases computationally feasible. The first study presented uses coarse-grained simulations to examine coupling between the two leaflets of a model membrane. While most publications report alignment of like domains, this study shows that lengthening the acyl chains of the high-melting-temperature phospholipid component or increasing the cholesterol concentration yields an alignment of unlike domains, accompanied by the appearance of a significant presence of cholesterol at the bilayer midplane, between the leaflets. The second study takes a different approach to leaflet coupling, engaging in atomistic simulations of compositionally asymmetric bilayers. Different lipids are present in each leaflet of the plasma membrane, so an asymmetric composition offers a more physiological model. The work reveals that even a single-phase leaflet is coupled to a phase-separated leaflet, as it adopts slightly different physical properties in the regions interacting with different domains. This finding suggests that transmembrane communication through coupling can occur in cells. Finally, the third study considers the role of ions in clusters of phosphatidylinositol 4,5-bisphosphate (PIP2), a lipid that makes up a small fraction of the plasma membrane but plays an outsize role in cell signaling and the retrovirus lifecycle. It confirms experimental evidence that clusters form in the presence of divalent cations but not monovalent ones and examines the interaction of ions and lipids and the impact on the lipids' physical properties.
An overview of recent experimental and theoretical developments in the field of the physics of membranes, including new insights from the past decade. The author uses classical thermal physics and physical chemistry to explain our current understanding of the membrane. He looks at domain and 'raft' formation, and discusses it in the context of thermal fluctuations that express themselves in heat capacity and elastic constants. Further topics are lipid-protein interactions, protein binding, and the effect of sterols and anesthetics. Many seemingly unrelated properties of membranes are shown to be intimately intertwined, leading for instance to a coupling between membrane state, domain formation and vesicular shape. This also applies to non-equilibrium phenomena like the propagation of density pulses during nerve activity. Also included is a discussion of the application of computer simulations on membranes. For both students and researchers of biophysics, biochemistry, physical chemistry, and soft matter physics.
This volume contains a comprehensive overview of peptide-lipid interactions by leading researchers. The first part covers theoretical concepts, experimental considerations, and thermodynamics. The second part presents new results obtained through site-directed EPR, electron microscopy, NMR, isothermal calorimetry, and fluorescence quenching. The final part covers problems of biological interest, including signal transduction, membrane transport, fusion, and adhesion. Key Features * world-renowned experts * state-of-the-art experimental methods * monolayers, bilayers, biological membranes * theoretical aspects and computer simulations * rafts * synaptic transmission * membrane fusion * signal transduction
