Chapter Three - Membrane-Mimetic Inverse Bicontinuous Cubic Phase Systems for Encapsulation of Peptides and Proteins

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Abstract

Inverse bicontinuous lipidic cubic phase materials have found a number of promising applications utilizing their unique three-dimensional structure, high thermodynamic stability, and surface area to volume ratios, together with their membrane-mimetic properties. Furthermore, they possess the ability to encapsulate a wide range of peptides and proteins, often with retention of native conformations and activity. Within peptide/protein-cubic phase systems, a complex structural relationship exists between the host lipid and the encapsulated biomolecule and, thus, a thorough understanding of the resulting structural changes with respect to both the mesophase and the encapsulated biomolecule is required, particularly in applications such as in meso crystallization and drug delivery. We present a summary of the properties, applications, and characterization methods of peptide/protein-cubic phase systems, as well as a review of the structural trends and considerations found in the current literature.

Section snippets

Inverse Bicontinuous Cubic Phases

The inverse bicontinuous cubic phases (QII phases) of amphiphile-aqueous solution systems, have found application in the fields of soft materials, biochemistry, physical chemistry, and biotechnology due to their unique properties and are increasingly used for encapsulation of proteins and peptides [1]. In particular these phases are being used for in meso crystallization and drug delivery [2], [3], [4], both of which will be discussed later in the chapter. The inverse bicontinuous cubic phases

Peptide and Protein Encapsulation: Understanding the Structural Relationship Between Guest Molecules and the Cubic Phase

End-use applications of the lipidic cubic phase, whether in biochemistry, biotechnology, or drug delivery, often depend upon the successful encapsulation of proteins or peptides. However, the complex structural relationship between the individual components of the system must be well understood if we are to make full use of these materials (Fig. 2). First, the mesostructure of the cubic phase is heavily dependent upon the chemical structure of individual lipid molecules, reflected in factors

Lipid Packing, Interfacial Curvature, and Lateral Pressure

Physicochemical parameters of the lipid mesophase, including lipid packing, interfacial curvature, and lateral pressure, significantly affect its ability to encapsulate proteins and peptides [34], [35]. The structure and geometry of self-assembled lipid phases, in particular the intrinsic monolayer curvature, are determined predominately by the three-dimensional structure and shape of the lipid itself, which can be expressed in terms of the CPP from Israelachvili and Mitchell [36] and

Applications of Bicontinuous Cubic Phases for Protein or Peptide Encapsulation

The encapsulation of proteins and peptides, and the structural effect they exert on the bicontinuous cubic phase is of particular importance when considering their end-use applications, which typically rely on retention of specific cubic phase symmetries, as well as reliable encapsulation of peptides and proteins, often with retention of specific conformations and preservation of activity. Therefore, we briefly describe the two main applications of such materials, in meso crystallization and

Cubic Phase Nanoparticles (Cubosomes)

The coexistence of the inverse bicontinuous cubic phase in excess water allows for the production of cubic phase nanoparticles. First reported in 1989, these nanoparticles, termed cubosomes, consist of small lipid-based nanoparticles typically ~ 100–400 nm, which retain both the triply periodic minimal surface geometry of the bulk cubic phase as well as the ability to encapsulate peptides and proteins [25]. As such, they broaden the range of applications for the protein-encapsulated lipidic cubic

Characterization of Bicontinuous Cubic Phase-Peptide/Protein Systems

Most studies characterizing protein encapsulation within the cubic phase have relied heavily on the technique of small angle X-ray scattering (SAXS). Its great utility stems from the fact that in aqueous lipid samples both the phase and the lattice parameter, a measure of unit cell size, can be determined with little effort [81]. Resolution and analysis time can be improved through the use of high flux synchrotron radiation, as well as high-throughput methodologies [74], [82], [83], [84], [85].

Conclusion

The encapsulation of peptides and proteins in the lipidic bicontinuous cubic phase has been demonstrated to induce a number of structural changes, which affect the material properties for end-use applications, while also providing broader information regarding the interactions between biomolecules and the lipid bilayer. The nature of these structural changes is highly dependent on lipid and bilayer properties, including the hydrophobic lipid chain size, resulting bilayer thickness and, by

Acknowledgments

T.G.M. was the recipient of a CSIRO-Melbourne Research Scholarship. Figures were produced with the assistance of MarvinSketch 16.8.8, 2016, ChemAxon (http://www.chemaxon.com); Qutemol 0.4.1, 2007 [129]; K3DSurf 0.6.2, 2007; and Blender 2.77, 2016.

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