Abstract
Protein biomaterials offer several advantages over those made from other components because their amino acid sequence can be precisely controlled with genetic engineering to produce a diverse set of material building blocks. In this work, three different elastin-like polypeptide (ELP) sequences were designed to synthesize pH-responsive protein vesicles. ELPs undergo a thermally induced hydrophobic transition that enables self-assembly of different kinds of protein biomaterials. The transition can be tuned by the composition of the guest residue, X, within the ELP pentapeptide repeat unit, VPGXG. When the guest residue is substituted with an ionizable amino acid, such as histidine, the ELP undergoes a pH-dependent hydrophobic phase transition. We used pH-responsive ELPs with different levels of histidine substitution, in combination with leucine zippers and globular, functional proteins, to fabricate protein vesicles. We demonstrate pH-dependent self-assembly, diameter, and disassembly of the vesicles using a combination of turbidimetry, dynamic light scattering, microscopy, and small angle X-ray scattering. As the ELP transition is dependent on the sequence, the vesicle properties also depend on the histidine content in the ELP building blocks. These results demonstrate the tunability of protein vesicles endowed with pH responsiveness, which expands their potential in drug-delivery applications.
| Original language | English |
|---|---|
| Pages (from-to) | 3678-3687 |
| Number of pages | 10 |
| Journal | Biomacromolecules |
| Volume | 23 |
| Issue number | 9 |
| DOIs | |
| State | Published - Sep 12 2022 |
Funding
This research was financially supported by the National Science Foundation Division of Materials Research, under award number 1709428, and M.T. Campagna. The authors gratefully acknowledge Profs. D.A. Tirrell and K. Zhang for AF-IQ E. coliand Z -ELP plasmid, Dr. Wellington Leite for training and assistance with SAXS, and Jamellah Jackson for her assistance with characterization. This work was performed in part at the Georgia Tech Institute for Electronics and Nanotechnology, a member of the National Nanotechnology Coordinated Infrastructure, which is supported by the National Science Foundation (grant no. ECCS-2025462). We wish to acknowledge the core facilities at the Parker H. Petit Institute for Bioengineering and Bioscience at the Georgia Institute of Technology for the use of their shared equipment, services, and expertise. Funding for the CSMB, which supports the SAXS instrument used, is provided by the Office of Biological & Environmental Research in the Department of Energy’s Office of Science. A portion of this research used resources at the High Flux Isotope Reactor and the Spallation Neutron Source, a DOE Office of Science User Facility operated by the Oak Ridge National Laboratory. R