Self-assembly of lyotropic liquid crystals: from fundamentals to applications
By Raffaele Mezzenga
The following article is based on a presentation by Raffaele Mezzenga, the 2011 AOCS Young Scientist Research Award winner. Mezzenga gave the address at the 102nd AOCS Annual Meeting & Expo, held in Cincinnati, Ohio, USA, May 1–4, 2011.
How and why do lipids and water organize into complex structures at nanometer-length scales? What is the driving force behind this marvelous self-organization? This is a crucial question, whose relevance spans fields from biology to nanotechnology, cosmetics, and food technologies. To understand how nature does things, it is always instructive to use synthetic simplified analogs as model systems. In the case of lyotropic liquid crystals, the approach has been very inspiring, because it has helped us learn from the self-assembly processes that take place in synthetic block copolymers in the solid state. This has opened a new avenue toward the design of synthetic complex organic fluids. As a result, block copolymers have become a major field of research in polymer physics and technology.
The very same structures that macromolecular scientists have been manipulating for about 30 years with the help of synthetic templates have been designed by nature to a greater level of perfection for millions of years using two very fundamental biological building blocks: water and lipids. These two components, which in living matter represent the main constituents of a cell’s bulk and surface, are also the main components of self-assembled food mesophases. In these systems, the water partitions with the lipid polar heads and microphase separates from the apolar lipid tail at a molecular-length scale. This gives rise to structured fluids, in which the spatial periodicity is similar to that of an inorganic crystal, but with a spatial arrangement that is one order of magnitude larger (~10 Å). Typical examples of food mesophases based on self-aggregating water and lipids are found at the water-oil interface of food emulsions, such as mayonnaise and salad dressing. Such self-aggregating mesophases can have an important role in stabilizing the droplet interfaces.
The exact typology of a mesophase crystal structure depends on which point of the temperature-composition phase diagram is considered. Precise experimental phase diagrams exist for the most common lipid-water mixtures, such as those occurring in monoglycerides. A typical phase diagram and the most common liquid crystalline mesophases encountered in foods are shown in Fig. 1. Although experimental techniques such as X-ray diffraction can determine very accurately the boundaries of these phase diagrams, unlike their synthetic analogs, no theoretical tools that allow the prediction of the phase diagrams of lipid-water systems exist to date.
Despite their apparent simplicity, lipids and water are a challenging system to understand at the molecular level. Water is the most complex solvent that one can possibly face, as the multiple hydrogen bonds that occur among water molecules can already be viewed as a structured fluid in which clusters of water molecules are bound together for very short times. In the case of uncharged polar liquids, water can also directly interact via hydrogen bonds with the polar heads of the lipid, and this complex self-aggregating behavior determines to a great extent the phase behavior of the resulting self-assembled systems. This complex behavior has been recognized since the 1960s but only recently has a real quantitative description of this self-associating process started to emerge.
From a practical point of view, predicting the exact phase diagram of lipid-water systems is the very first starting point in designing processed foods based on these molecules. One of the most striking differences in the physical properties of self-assembled food mesophases is their rheological properties. Within a very narrow range of water concentration and temperature, the viscosity and the hardness of these phases can change by more than one million times. Indeed, although none of the observable mesophases can be viewed as purely viscous or elastic, either the first or the second behavior can clearly dominate. For example, bicontinuous cubic phases are a tough viscoelastic solid in which the elasticity is comparable with that of standard rubber. This is a remarkable fact if one considers that in rubbers, hardness is built up by inducing cross-links among macromolecules to increase the molecular weights up to tens, hundreds, or thousands of thousands (104–106) of daltons per mole. In lipid-water self-assembled mesophases, the highest molecular weight is that of the lipid molecule itself, which is typically always below a few hundreds (102) of daltons per mole. Nevertheless, by just moving the phase diagrams in toward reversed hexagonal phases, one readily reaches a region where the mesophases are able to flow, and they become similar to a very viscous oil. Understanding this is of prime importance when designing a food based on self-assembled lipid and water, as it will eventually directly affect the mouthfeel that the food generates.
Another very important reason to predict the exact mesophase structures is that one may be able to produce functional liquid products that carry dispersed and suitably designed mesophases within them. This can essentially be accomplished by redispersing bulk mesophase droplets of 500–2000 Å into any water environment and stabilizing the droplet interfaces by a suitable food emulsifier. High-magnification transmission electron microscopy images of a few dispersed mesophase droplets in water are shown in Figure 2. If the droplets are smaller than the wavelength of light (typically <1500 Å), the liquid product will remain completely transparent. Because these mesophases are internally divided into hydrophilic (water plus the polar lipid heads) and hydrophobic (lipid tails) domains, these systems constitute ideal carriers for delivering hydrophilic nutrients. They can also protect fragile hydrophobic drugs from the external water environment, thus reducing their exposure to oxidative processes. Because the ability to encapsulate nutrients by these internally structured colloidal dispersions also depends on the ratio between the size of the guest molecule and that of the hosting hydrophilic/hydrophobic compound, it becomes crucial to predict accurately the topologies of the mesophases under controlled conditions. Furthermore, not all mesophases can be redispersed in water; only those that can coexist at thermodynamic equilibrium with water can do so. Typically only reversed bicontinuous cubic phases and hexagonal phases show these features, whereas lamellar phases can exist only at limited hydration conditions.
<>A crucial property of such mesophases is that the diffusion-based release processes of nutrients encapsulated within them are dependent on the structures of the specific mesophase. Very recently this property has been exploited in my group to design a new class of liquid crystalline foods based solely on lipids that are capable of responding in an “intelligent” way to the pH changes of the gastrointestinal tract. More specifically, these lipidic mesophases can readjust in structure and self-organize into a reverse hexagonal phase at a pH of 2, to retain a specific drug from a premature release in the stomach. Then, in the neutral pH environment of the intestine (pH 7), the mesophase readapts into a reverse cubic phase characterized by a fast release, and the specific drug targeted to the intestinal tract is released. Figure 3 illustrates the concept behind these newly developed responsive foods. This “smart” stimuli-responsive behavior of complex food systems based solely on lipid and water opens new possibilities that were inconceivable a few years ago. Paradoxically, while the chemistry of fat and water has been known for a long time, our understanding of self-assembly in lipidic mesophases and its potential in modern processed foods is only beginning. Combining newly available theoretical and experimental techniques to study these interesting complex food systems will open new avenues toward functional foods.
Raffaele Mezzenga is professor of food and soft materials at the Swiss Federal Institute of Technology in Zurich, Switzerland. He can be reached at firstname.lastname@example.org.
1. Mezzenga, R., Self-assembled food mesophases, in Research Worlds—Focus on Food, Alimentarium Foundation Editions (March 2009).
2. Leibler, L., Theory of microphase separation in block copolymers, Macromolecules 13:1602–1617 (1980).
3. Mezzenga, R., P. Schurtenberger, A. Burbidge, and M. Michel, Understanding foods as soft materials, Nat. Mat. 4:729–740 (2005).
4. Qiu, H., and M. Caffrey, The phase diagram of the monoolein/water system: metastability and equilibrium aspects, Biomaterials 21:223–234 (2000).
5. Lee, W.B., R. Mezzenga, and G.H. Fredrickson, Anomalous phase sequences in lyotropic liquid crystals, Phys. Rev. Lett. 99:187801–187804 (2007).
6. Sagalowicz, L., R. Mezzenga, and M.L. Leser, Investigating reversed liquid crystalline mesophases, Curr. Opin. Colloid Interface Sci. 11:224–229 (2006).
7. Negrini, R., and R. Mezzenga, pH-Responsive lyotropic liquid crystals for controlled drug delivery, Langmuir 27:5296–5303 (2011).