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Solutions of rigid rods display orientational and/or positional order at appropriate concentrations. Model systems of rigid rods are formed by Tobacco Mosaic Virus (TMV) in water or dilute salt solutions. In pure water, TMV particles are strongly negatively charged and electrostatic repulsion orders the virus into three-dimensional crystals with both orientational and positional order. When salt is added to the system, electrostatic repulsion is screened and the TMV particles lose much of their positional order, but retain their orientational order and form a nematic liquid crystal phase.The long and short-range order of TMV solutions is best studied using freeze- fracture replication TEM. Each virus, which is the equivalent of a single molecule in a normal crystal or liquid crystal, is easily visualized as a discrete particle (TMV are approximately 300 nm long and 18 nm in diameter).

The rheological and mechanical properties of crosslinked polymer gels arise from the structure of the gel network. In turn, the structure of the gel network results from: thermodynamically determined interactions between the polymer chain segments, the interactions of the crosslinking metal ion with the polymer, and the deformation history of the network. Interpretations of mechanical and rheological measurements on polymer gels invariably begin with a conceptual model of,the microstructure of the gel network derived from polymer kinetic theory. In the present work, we use freeze-etch replication TEM to image the polymer network morphology of titanium crosslinked hydroxypropyl guars in an attempt to directly relate macroscopic phenomena with network structure.

In standard dehydration and epoxy embedding of biological material, substantial portions of lipid are extracted. In addition, the mechanisms of lipid fixation by osmium tetroxide are either unknown or poorly understood. Liposomes, particles of lamellar liquid crystalline lipid in water, react immediately with osmium, but are not preserved and the bulk of the lipid is removed in subsequent processing. Several authors heve attempted to improve lipid retention by using water-soluble embedding media, various dehydration techniques, etc., with varying degrees of success. The structure and morphology of the lipid bilayers in tissue or in liposomes remains open to question. To deal with these problems, a new type of lipid which can be polymerized was developed. The synthetic lipid, N,N dimethyl, di(ethoxycarbonyl-2,4-hexadecadienyl)ammonium iodide, DDEAI, incorporates a polymerizable conjugated diene moeity in each tail of the molecule. The counterion in the head group is iodide, which provides a strong, yet localized electron scattering site which precludes the need for other stains (Fig. 1.).

An optimal drug delivery vehicle should circulate in the body long enough to reach the site of illness or disease and also localize itself at the desired site to consequently deliver its contents at a rate appropriate for maximum therapeutic benefit. It should also possess a large drug loading capacity and retain its contents over the course of treatment. While liposomal systems have experienced success with extending circulation, content retention and controlled release remain problematic. The vesosome - a large lipid bilayer enclosing many smaller liposomes - is the most suitable candidate for addressing these issues. The external lipid bilayer offers a second barrier of protection for interior components and also serves as the anchor for active targeting components. Furthermore, internal compartmentalization permits customization of separate environments for multiple therapeutics and release triggers, highlighting the vesosome's potential as a single site, single dose, multiple component drug treatment.To assess the viability of the vesosome as a drug carrier, its in vivo lifetime and biodistribution was examined in live animals. Our work examines how these properties are affected by lipid composition and the addition of other functional components, including ones for controlled release and active targeting.

Although the presence of cholesterol, the major neutral lipid component, is well known in native surfactants (upto 10 % mass), its role in the surfactant remains uncertain. The most recently FDA approved clinical surfactant contain cholesterol, while two that have been used for 20 years have cholesterol carefully removed. However, they are all successful in treating neonatal respiratory distress syndrome (NRDS) resulting from a lack of surfactant. As a result the optimal concentration of cholesterol, if any at all, remains debated. Here we present indications for an optimal cholesterol concentration by presenting alterations to the phase and morphology of Survanta, a clinically used bovine lung surfactant extract, induced by both physiological and elevated concentrations of cholesterol when the monolayer is in contact with surfactant in the subphase. We find that low cholesterol concentrations (1-2 wt %) help to achieve a lower surface tension by enhancing surfactant material adsorption to the interface. However, increasing the cholesterol concentrations to higher values (≈ 20 wt %) significantly alters the normal surfactant isotherm. Alterations in a typical signature plateau for Survanta at ∼ 40 mN/m are noted suggesting a change in the solid phase fraction of the film. Fluorescence microscopic imaging reveals the coexistence of discrete monolayer along with “multilayer reservoir” adjacent to the air/water interface. Differences in the collapse structures of the monolayer are also noted indicating an alteration in the mechanical properties of the monolayer film. Alterations in these properties in the absence of surface active lung surfactant proteins were also observed indicating that interactions between the monolayer at the interface, the “multilayer reservoir” and the subphase are essential for the proper functioning of the lung surfactant.

One of the essential features of healthy lung surfactant (LS) is to reduce the surface tension as well as increases the surface viscosity at the alveolus air-water interface to prevent the collapse. Currently, there is no simple theory explaining physicochemical properties of a monolayer with respect to surface tension or surface viscosity in the dynamic process of breathing. Monitoring the viscoelastic properties of interfacial films allows to predict how such a property depends on lipid and protein composition, packing properties and other variables at different states of the breathing process. Cholesterol and proteins are believed to have drastic effects on lung surfactant system by changing surface shear viscosities but systematic studies regarding this have not been done yet and the compositional effects remained still unkown. Here we focus on the influence of (1) cholesterol and (2) LS proteins such as SP-BMini and SP-Cff on the surface viscosity and surface tension of pure DPPC monolayer as well as the lung surfactant replacement Survanta.In order to study the compositional effects on the surface viscosity and surface tension, we have used custom-made Langmuir trough as a viscometer. Our viscometer consists of a Langmuir trough equipped with Helmholz coils which generate a controlled magnetic force to move a magnetic needle floating on the monolayer. The viscometer enables to examine the surface viscosity and surface tension as well as morphological changes in a LS monolayer as varying the amount of cholesterol and LS proteins. Atomic force microscopy has been also used to further investigate the morphological changes of a LS monolayer in nanometre regime after prepared by Langmuir Blodgett technique.

Lung surfactant (LS) is a mixture of lipids and proteins that lines the air-water interface of the alveolar walls. It modulates the surface tension in the lungs which greatly reduces the mechanical work of breathing and also prevents the collapse of the alveoli upon expiration. Although lipids are the major constituent of LS, the hydrophobic surfactant proteins SP-B and SP-C play an integral role in proper adsorption of LS to the air-water interface. Understanding the role of these proteins will allow for better design of exogenous LS therapies for the treatment of respiratory distress syndrome. Confocal microscopy's abilities to optically section a sample and simultaneously image multiple dyes provide an ideal tool to study LS adsorption in vitro. Combining three-dimensional, multi-component imaging with surface tension measurements allows us to determine whether a particular surfactant mixture can successfully transition from bilayer aggregates in the bulk to a functional monolayer on the interface. SP-B and SP-C are believed to play an integral role in both the transport of aggregates to the interface and the unfolding of surfactant bilayers into a monolayer. Confocal microscopy has allowed us to study the importance of lipid and protein composition on the transport and unfolding of LS.

Lipid domains indicate the coexistence of thermodynamic phases of lipid molecules at hydrophobic-hydrophilic interface. Domain size, shape and distribution are directly affected by the line tension (λ) and dipole density difference (m) at domain boundaries [1-2]. In this work, a thermodynamic equation expressing domain size distribution was derived and fitted to domain distributions from fluorescence images of both healthy (control) and experimental allergic encephalomyelitis (EAE) cytoplasmic (CYT) model myelin monolayers. From these fits we simultaneously extract λ (in units of fN) and m (in units of pC/m2). Both parameters λ and m decrease with increasing surface pressure (Π). Moreover, the control monolayer had higher values of λ and m compare with EAE monolayer for all values of Π where domains can be observed clearly. Based on the difference of these values, EAE monolayer seems to be more ‘stressed’ than control monolayer. This indicates an important relationship between Π, domain size and distribution, λ and m, which can be used to point out the potential cause of demyelinating diseases like Multiple Sclerosis (MS) at molecular scale.