Protein Vesicles with pH-Responsive Disassembly

Dautel, Dylan R.; Heller, William T.; Champion, Julie A.

doi:10.1021/acs.biomac.2c00562

Protein Vesicles with pH-Responsive Disassembly

Journal Article · Tue Aug 09 00:00:00 EDT 2022 · Biomacromolecules

DOI:https://doi.org/10.1021/acs.biomac.2c00562· OSTI ID:1887670

Dautel, Dylan R. ^[1]; ^[2]; ^[1]

Georgia Institute of Technology, Atlanta, GA (United States)
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

We report 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.

View Accepted Manuscript (DOE)

Research Organization:: Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)

Sponsoring Organization:: National Science Foundation; USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: AC05-00OR22725

OSTI ID:: 1887670

Journal Information:: Biomacromolecules, Journal Name: Biomacromolecules Journal Issue: 9 Vol. 23; ISSN 1525-7797

Publisher:: American Chemical SocietyCopyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
elastin-like polypeptides
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Protein Vesicles with pH-Responsive Disassembly

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