FUNCTIONALIZED SYNTHETIC LIPIDS AS MOLECULAR TOOLS FOR CELL SURFACE ENGINEERING
Abstract
Natural glycolipids can insert from the extracellular environment into cell membranes, providing an opportunity for modifying the cell surface with various molecular fragments. However, natural glycolipids have several limitations: they are difficult to isolate from natural sources or obtain by chemical or chemoenzymatic synthesis, and their physical properties such as poor solubility in aqueous media are incompatible with experiments involving live cells. To overcome these limitations, a technology based on functionalized synthetic lipids, also known as FSL constructs (FSL: Function-Spacer-Lipid), was developed. FSLs are built from several structural blocks: a functional part, i.e., a glycan or another molecular fragment to be introduced onto the membrane surface, a spacer-arm, and a lipid anchor. FSLs insert into cell membranes without adversely affecting cell viability or functioning, and the membrane density of inserted FSLs can be varied making the process of modification controllable. The functional part of an FSL is actually any molecular fragment, which is required to be introduced onto the surface of the cell. The range of functional parts includes glycans, peptides, proteins, oligonucleotides, fluorescent labels, chelating groups, biotin, and reactive groups for click conjugation. Along with linear FSLs, various types of multiantennary constructs with complex architecture bearing several functional parts (same or different) have been synthesized. Short adipic or aminovaleric fragments were initially used as spacer-arms in FSLs. Later spacers of the carboxymethylglycine (CMG) family were introduced. CMG spacer-arms maintain an extended linear conformation thus distancing the functional part from the membrane and making it more accessible for receptor binding. The negative charge of CMG spacers also improves solubility in aqueous media expanding the range of functional parts to hydrophobic moieties such as biotin or fluorescent dyes. The most commonly used lipid anchor of FSLs is dioleoylphosphatidylethanolamine (DOPE).
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