Self-assembly of tunable intrinsically disordered peptide amphiphiles

DOI: 10.1021/acs.biomac.2c00866

Authors: Tamara Ehm (Tel Aviv University; Ludwig-Maximilians-Universität; Tel Aviv University) , Hila Shinar (Tel Aviv University) , Guy Jacoby (Tel Aviv University) , Sagi Meir (Tel Aviv University) , Gil Koren (Tel Aviv University) , Merav Segal Asher (Tel Aviv University) , Joanna Korpanty (Northwestern University) , Matthew P. Thompson (Northwestern University) , Nathan C. Gianneschi (Northwestern University) , Michael M. Kozlov (Tel Aviv University) , Salome Azoulay-Ginsburg (Tel Aviv University) , Roey J. Amir (Tel Aviv University) , Joachim O. Rädler (Ludwig-Maximilians-Universität) , Roy Beck (Tel Aviv University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Biomacromolecules

State: Published (Approved)
Published: December 2022
Diamond Proposal Number(s): 21971 , 24693 , 29428 , 28723 , 28010

Abstract: Intrinsically disordered peptide amphiphiles (IDPAs) present a novel class of synthetic conjugates that consist of short hydrophilic polypeptides anchored to hydrocarbon chains. These hybrid polymer-lipid block constructs spontaneously self-assemble into dispersed nanoscopic aggregates or ordered mesophases in aqueous solution due to hydrophobic interactions. Yet, the possible sequence variations and their influence on the self-assembly structures are vast and have hardly been explored. Here, we measure the nanoscopic self-assembled structures of four IDPA systems that differ by their amino acid sequence. We show that permutations in the charge pattern along the sequence remarkably alter the headgroup conformation and consequently alter the pH-triggered phase transitions between spherical, cylindrical micelles and hexagonal condensed phases. We demonstrate that even a single amino acid mutation is sufficient to tune structural transitions in the condensed IDPA mesophases, while peptide conformations remain unfolded and disordered. Furthermore, alteration of the peptide sequence can render IDPAs to become susceptible to enzymatic cleavage and induce enzymatically activated phase transitions. These results hold great potential for embedding multiple functionalities into lipid nanoparticle delivery systems by incorporating IDPAs with the desired properties.

Subject Areas: Biology and Bio-materials, Chemistry


Instruments: B21-High Throughput SAXS , I22-Small angle scattering & Diffraction

Other Facilities: SWING at SOLEIL; P12 at PETRA III

Added On: 07/12/2022 09:56

Documents:
acs.biomac.2c00866.pdf

Discipline Tags:

Biomaterials Chemistry Materials Science Organic Chemistry

Technical Tags:

Scattering Small Angle X-ray Scattering (SAXS)