Self-assembled molecules phospholipids

Liposomal formulations may also be used to deliver TLR4 agonists. Consisting of spherical vesicles formed by the self-assembly of phospholipid bilayers, liposomes are a versatile, biocompatible vaccine adjuvant formulation. The wide variety of available phospholipid molecules that are employed to make liposomes may have significant effects on the structure and biological activity of the adjuvant. 

Also, liposomes (see later) are very similar but are formed by the self-assembly of phospholipid molecules in an aqueous environment. The amphiphilic phospholipid molecules form a closed spherical bilayer in an attempt to shield their hydrophobic groups from the aqueous environment, whilst still maintaining contact with the aqueous phase via the hydrophilic head group. The resulting closed sphere may encapsulate water-soluble drugs within the inner aqueous compartment or may encapsulate lipid soluble drugs within the bilayer membrane. Alternatively, lipid soluble drugs may be complexed with a hydrophilic cyclodextrin and then encapsulated within the liposome aqueous compartment. 

When the induced membrane potential exceeds a certain threshold value, the dielectric breakdown occurs. The dielectric breakdown generates pores in the phospholipid cell membrane. These pores are generated reversibly, and they are sealed spontaneously with the self-assembly of phospholipid molecules. The amount of membrane potential required to initiate electroporation is known to be approximately 1 V. 

When placed in aqueous solution, phospholipids spontaneously form a lipid bilayer (Figure 26.13) in which polar head groups lie on the surface, giving the bilayer an ionic coating. Nonpolar hydrocarbon chains of fatty acids lie buried within the bilayer. This self-assembly of phospholipids into a bilayer is a spontaneous process driven by two types of noncovalent forces (1) hydrophobic effects, which result when nonpolar hydrocarbon chains cluster together and exclude water molecules and (2) electrostatic interactions, which result when polar head groups interact with water and other polar molecules in the aqueous environment. 

In this chapter, we have surveyed a wide range of chiral molecules that self-assemble into helical structures. The molecules include aldonamides, cere-brosides, amino acid amphiphiles, peptides, phospholipids, gemini surfactants, and biological and synthetic biles. In all of these systems, researchers observe helical ribbons and tubules, often with helical markings. In certain cases, researchers also observe twisted ribbons, which are variations on helical ribbons with Gaussian rather than cylindrical curvature. These structures have a large-scale helicity which manifests the chirality of the constituent molecules. 

It was mentioned that ordinary surfactants (soaps, etc.), when dissolved in water, form self-assembly micellar structures. Phospholipids are molecules like surfactants they also have a hydrophilic head and generally have two hydrophobic alkyl chains. These molecules are the main components of cell membranes. Lung fluid also consists mainly of lipids of this kind. In fact, usually, cell membrane are made up of two layers of phospholipids, with the tails turned inward, in an attempt to avoid water. The external membrane of a cell contains all the organelles and the cytoplasm. 

It is not yet understood how life began on Earth nearly four billion years ago, but it is certain that at some point very early in evolutionary history life became cellular. All cell membranes today are composed of complex amphiphilic molecules called phospholipids. It was discovered in 1965 that if phospholipids are isolated from cell membranes by extraction with an organic solvent, then exposed to water, they self-assemble into microscopic cell-sized vesicles called liposomes. It is now known that the membranes of the vesicles are composed of bimolecular layers of phospholipid, and the problem is that such complex molecules could not have been available at the time of life s beginning. Phospholipids are the result of a long evolutionary process, and their synthesis requires enzymatically catalyzed reactions that were not available for the first forms of cellular life. 

Even newer generations of nanomaterials are based on carbon nanotubes using the bottom-up approach. The materials are still very expensive, but the technology is evolving rapidly. Another type of nanotube has been prepared based on self-assembly of specific molecules such as chitosan-based nanoparticles of polypeptides, DNA or synthetic polymers. Phospholipids or dendrimer-coated particles are suitable for the entrapment of actives in very small vesicles. The current materials are still lacking in selectivity and yield (costs). 

Life sciences provide a fascinating array of examples in which colloid and surface science plays a vital (pun intended ) role in maintaining and promoting supramolecular structures and processes that sustain life. A specific example is the phospholipid bilayers that form the walls of biological cells and separate the interior of the cells from the rest of the environment (see Fig. 1.2 see also Chapter 8, Section 11). These bilayers arise from self-assembly of component molecules, each of which consists of a hydrophilic head group... 

Artificial membranes are used to study the influence of drug structure and of membrane composition on drug-membrane interactions. Artificial membranes that simulate mammalian membranes can easily be prepared because of the readiness of phospholipids to form lipid bilayers spontaneously. They have a strong tendency to self-associate in water. The macroscopic structure of dispersions of phospholipids depends on the type of lipids and on the water content. The structure and properties of self-assembled phospholipids in excess water have been described [74], and the mechanism of vesicle (synonym for liposome) formation has been reviewed [75]. While the individual components of membranes, proteins and lipids, are made up of atoms and covalent bonds, their association with each other to produce membrane structures is governed largely by hydrophobic effects. The hydrophobic effect is derived from the structure of water and the interaction of other components with the water structure. Because of their enormous hydrogen-bonding capacity, water molecules adopt a structure in both the liquid and solid state. 

Although it is clear that complex lipids can be synthesized under laboratory simulations using pure reagents, the list of required ingredients does not seem plausible under prebiotic conditions. Therefore, it is unlikely that early membranes were composed of complex lipids such as phospholipids and cholesterol. Instead, there must have been a source of simpler amphiphilic molecules capable of self-assembly into membranes. One possibility is lipidlike fatty acids and fatty alcohols, which are products of FTT simulations of prebiotic geochemistry [12] and are also present in carbonaceous meteorites. Furthermore, as will be discussed later, these compounds form reasonably stable lipid bilayer membranes by self-assembly from mixtures (Fig. 4a). 

Figure 1. (A) Schematic illustration of a phospholipid molecule with hydrophilic head and hydrophobic tail. Cross-sectional view of (B) the micelle structure and (C) the bilayer sheet structure built through the self-assembly of the lipid molecules (A).

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