Self-assembling Behavior of Designer Lipid-like Peptides

Abstract

Even though enormous progress has been made in our understanding of soluble proteins and enzymes, our knowledge of membrane proteins, particularly integral membrane proteins, still lags far behind. Although a large number of chemical detergents and lipids are available, so far they are inadequate for tackling the problem of solubilizing and stabilizing membrane proteins outside of the lipid bilayer. Thus, the development of new detergents and lipid-like molecules is an important prerequisite for solving those problems. We have designed a class of lipid-like peptides that are less than 10 natural amino acids in length and structurally amphiphilic. Each peptide consists of a hydrophilic head-group composed of charged or polar residues and a hydrophobic tail consisting of a string of hydrophobic amino acids. In aqueous solutions, they self-organize to form different supramolecular structures such as vesicles, nanotubes or membranes. It has been shown that they stabilize the functions of several membrane proteins against environmental stresses such as heat and drying. We here report the self-assembling behavior of several designer lipid-like peptides at different peptide concentrations, using dynamic light scattering and fluorescence measurements. These peptides exhibit self-assembling behavior akin to some lipids, with distinct critical aggregate concentration (CAC) values and sequestration of the hydrophobic tails away from water. These values depend on the peptide sequence, with more hydrophobic peptides having lower CAC values. This information will be essential in using the lipid-like peptides for membrane protein stabilization and structural studies.

Keywords:

• Self-assembly
• Lipid-like peptides
• Proteins
• Enzymes
• Surfactant peptides
• Membrane proteins

Acknowledgements

We thank members in of our laboratory for helpful and stimulating discussions. This work is supported in part by grants from the Multidisciplinary University Research Initiative (MURI)/AFOSR, and the National Science Foundation to the Center for Bits & Atoms to the Massachusetts Institute of Technology.