Liposomes for DNA Nanotechnology: Preparation, Properties, and Applications - DNA Nanotechnology: From Structure to Function - page 57

Fig. 4.1 ( a ) Schematic shows self-assembly of lipid molecules into lipid bilayers and liposomes.
Both hydrophobic and hydrophilic molecules can be contained in liposomes as respectively marked
by 1 and 2 .( b ) The thickness of a lipid bilayer is around 5 nm and molecular structure of the
amphiphilic DOPC is shown

4.2 Structure of Lipids and Liposomes

Bangmen et al. were the first to report the spontaneous formation of vesicles upon
addition of phospholipids to an aqueous solution (Fig. 4.1 a) [ 11 ]. Hydrophobic
molecules can be loaded into the bilayer region marked by 1 , while hydrophilic
molecules can be entrapped in the compartment marked 2 . The bilayer thickness
is approximately 5 nm (Fig. 4.1 b). This process is driven by the even lower
solubility of bilayer-forming lipids compared to many other amphiphiles whose
critical micelle concentration (CMC) is 10 2 -10 4 M[ 12 , 13 ]. In addition, most
liposome-forming molecules can be modeled as a rod, disfavoring packing into the
micellar structure. The most commonly used phospholipids include zwitterionic
phosphatidylcholine (PC) and phosphatidylethanolamine (PE), negatively charged
phosphatidic acid (PA), phosphatidylglycerol (PG), and phosphatidylserine (PS)
(Fig. 4.2 ). Cationic lipids are uncommon in nature but can be prepared synthetically,
such as the commonly used 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)
[ 12 , 13 ].

4.3 Liposome Phase Transition

In addition to charge, the phase behavior of a lipid also strongly influences its
properties. Below the phase transition temperature (T c ), the hydrophobic tails are
extended and the lipids adopt a gel-like state, whereas above T c , the lipids are quite
mobile and adopt a liquid crystal or liquid-like state (Fig. 4.3 a). Using differential