Interactions with lipids

Bilayer phase transitions are sensitive to the presence of solutes that interact with lipids, including multivalent cations, lipid-soluble agents, peptides, and proteins. 

TABLE 6 Specific Features of S-Layer Proteins Governing Interactions with Lipid Membranes... 

Amphipathic peptides contain amino acid sequences that allow them to adopt membrane active conformations [219]. Usually amphipathic peptides contain a sequence with both hydrophobic amino acids (e.g., isoleucine, valine) and hydrophilic amino acids (e.g., glutamic acid, aspartic acid). These sequences allow the peptide to interact with lipid bilayer. Depending on the peptide sequence these peptides may form a-helix or j6-sheet conformation [219]. They may also interact with different parts of the bilayer. Importantly, these interactions result in a leaky lipid bilayer and, therefore, these features are quite interesting for drug delivery application. Obviously, many of these peptides are toxic due to their strong membrane interactions. 

New developments in immobilization surfaces have lead to the use of SPR biosensors to monitor protein interactions with lipid surfaces and membrane-associated proteins. Commercially available (BIACORE) hydrophobic and lipophilic sensor surfaces have been designed to create stable membrane surfaces. It has been shown that the hydrophobic sensor surface can be used to form a lipid monolayer (Evans and MacKenzie, 1999). This monolayer surface can be used to monitor protein-lipid interactions. For example, a biosensor was used to examine binding of Src homology 2 domain to phosphoinositides within phospholipid bilayers (Surdo et al., 1999). In addition, a lipophilic sensor surface can be used to capture liposomes and form a lipid bilayer resembling a biological membrane. 

The following sections discuss how polymers and polyplexes can be chemically designed to be bioresponsive in three key delivery functions (1) polyplex surface shielding, (2) interaction with lipid bilayers, and (3) polyplex stability. 

Yessine MA, Leroux JC (2004) Membrane-destabilizing polyanions interaction with lipid bilayers and endosomal escape of biomacromolecules. Adv Drug Deliv Rev 56 999-1021... 

Da Costa G, Mouret L, Chevance S, Le Rumeur E, Bondon A (2007) NMR of molecules interacting with lipids in small unilamellar vesicles. Eur Biophys J Biophy 36 933-942... 

The number of organic substituents also influences interaction with lipid bilayers. Diphenyltin chloride causes disturbances of the hydrophobic region of the lipid bilayer, triphenyltin chloride adsorbs to the head-group region, and tetraphenyltin does not partition into the lipid bilayer [235-237]. Similar results were found for the butylated tins [238]. In addition, the mono-butyltin was homogeneously distributed within the lipid bilayer [238]. 

Figure 2.8 is not well absorbed and mineral oil has also been used as a laxative. Although such molecules go into lipid membranes, they cannot get out the other side, i.e., enter the blood stream, because their water solubility is very low. Solids with very low water solubility have even more difficulty because solids cannot interact with lipid membranes as well as liquids. 

Neuvonen, P.J., Niemi, M. and Backman, J.T. (2006) Drug interactions with lipid-lowering drugs mechanisms and clinical relevance. Clinical Pharmacology and Therapeutics, 80, 565-581. 

A synthetic peptide has been designed to mimic the effects of viral fusogenic properties (114,115). It consists of 30 amino acids with the major repeat of Glu-Ala-Leu-Ala so, it is referred to as a GALA peptide. It undergoes a conversion from an aperiodic conformation at neutral pH and becomes an amphipathic alpha helix at pH 5. In the more acidic environment, the peptide interacts with lipid bilayers (114,115). GALA has been incorporated into transferrin-targeted liposome, with the effect of significantly... 

Cl. Camejo, G., Suarez, Z. M., and Munoz, V., The apolipoproteins of human plasma high density lipoprotein a study of their lipid-binding capacity and interaction with lipid monolayers. Biochim. Biophys. Acta 218, 155-166 (1970). 

Fig.3 A migrating zone of solute molecules (spots) interacting with lipid bilayers (rings) in a chromatographic or electrophoretic separation system. The free solute molecules move (arrows) relative to the liposomes or vesicles in a flow of eluent or in an electric field. The solute molecules may either partition into the membranes and diffuse between the external and internal aqueous compartments of the structures as depicted, or interact with the external surface of the membranes and stay outside.

Integral Proteins Are Held in the Membrane by Hydrophobic Interactions with Lipids... 

It appears that most of the protons that do not exchange are not shielded from water by hydrophobic interaction with lipids since the fraction of exchangeable protons in the amide bonds of residual protein after pronase treatment is approximately the same as in intact ghosts. Indeed this result, together with ORD data, suggests that there is no difference in the gross conformations of the enzymatically accessible and inaccessible protein. Proton exchange is probably inhibited because... 

Amino acids with nonpolar (hydrophobic) R-groups are generally found in the interior of proteins that function in an aqueous environment, and on the surface of proteins (such as membrane proteins) that interact with lipids. Amino acids with polar side chains are gener ally found on the outside of proteins that function in an aqueous environment, and in the interior of membrane-associated proteins. 

The linear polypeptide chains of a protein fold in a highly specific way that is determined by the sequence of amino acids in the chains. Many proteins are composed of two or more polypeptides. Certain proteins function in structural roles. Some structural proteins interact with lipids in membrane structures. Others aggregate to form part of the cytoskeleton that helps to give the cell its shape. Still others are the chief components of muscle or connective tissue. Enzymes constitute yet another major class of proteins, which function as catalysts that accelerate and direct biochemical reactions. 

Flavonoids and other polyphenols can interact with lipids and proteins. The interactions with proteins could be both unspecific or specific, meanwhile the interactions with lipids seems to be rather unspecific, based essentially on physical adsorption. This physical adsorption would mostly depend on the hydrophobic/hydrophilic characteristics of the flavonoid molecule, the number of hydroxyl substituents, and the polymerization degree [Erlejman et al., 2004 Verstraeten et al., 2005, 2003, 2004]. 

Flavonoids bear different degrees of hydroxylation, polymerization, and methylation that define both specific and nonspecific interactions with membrane lipids. Molecule size, tridimensional structure, and hydrophili-city/hydrophobicity are chemical parameters that determine the nature and extent of flavonoid interactions with lipid bilayers. The hydrophilic character of certain flavonoids and their oligomers endows these molecules with the ability to bind to the polar headgroups of lipids localized at the water-lipid interface of membranes. On the other hand, flavonoids with hydrophobic character can reach and cross the lipid bilayer. In this section, we will discuss current experimental evidences on the consequences of flavonoid interactions with both the surface and the hydrophobic core of the lipid bilayer. 

Uekusa Y, Kamihira M, Nakayama T. 2007. Dynamic behavior of tea catechins interacting with lipid membranes as determined by NMR spectroscopy. J Agric Food Chem 55 9986-9992. 

E. Interaction with Lipids and Membranes Involvement in Membrane Trafficking... 

---