How Peptide Molecular Structure and Charge Influence the Nanostructure of Lipid Bicontinuous Cubic Mesophases: Model Synthetic WALP Peptides Provide Insights.
Nanostructured bicontinuous lipidic cubic phases are used for the encapsulation of proteins in a range of applications such as in meso crystallization of transmembrane proteins and as drug delivery vehicles. The retention of the nanoscale order of the cubic phases subsequent to protein incorporation, as well as retention of the protein structure and function, is essential for all of these applications. Herein synthetic peptides (WALP21, WALPS53, and WALPS73) with a common α-helical hydrophobic domain, but varying hydrophilic loop size, were designed to systematically examine the effect of peptide structure and charge on bicontinuous cubic phases. The effect of the cubic phases on the secondary structure of the peptides was also investigated. The incorporation of the WALP peptides in cubic phases formed by a range of lipids showed that hydrophobic mismatch of the peptides with the lipid bilayers, the hydrophilic domain size, and peptide charge were all significant factors determining the response of the lipid nanomaterial to protein insertion. As charge repulsion had the most significant effect on the phase transitions observed, we suggest that buffer pH and salt concentration must be carefully considered to ensure cubic mesophase retention. Importantly, the WALP peptides were found to have a different conformation depending on the local lipid environment. Such structural changes could potentially affect membrane protein function, which is crucial for both current and prospective applications.
CSIRO Manufacturing , Clayton, Victoria 3168, Australia.
Leonie
L
van 't Hag
Xu
X
Li
CSIRO Manufacturing , Clayton, Victoria 3168, Australia.
Thomas G
TG
Meikle
Søren V
SV
Hoffmann
Nykola C
NC
Jones
Jan Skov
JS
Pedersen
Australian Synchrotron , Clayton, Victoria 3168, Australia.
Adrian M
AM
Hawley
Sally L
SL
Gras
School of Science, College of Science, Engineering and Health, RMIT University , Melbourne, Victoria 3001, Australia.
Charlotte E
CE
Conn
CSIRO Manufacturing , Clayton, Victoria 3168, Australia.|School of Science, College of Science, Engineering and Health, RMIT University , Melbourne, Victoria 3001, Australia.
Calum J
CJ
Drummond
D008051:Lipid Bilayers / Q000737:chemistry*; D008958:Models, Molecular; D049329:Nanostructures / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary
D008051:Lipid Bilayers; D010455:Peptides