Order from Disorder with Intrinsically Disordered Peptide Amphiphiles

Guy Jacoby, Merav Segal Asher, Tamara Ehm, Inbal Abutbul Ionita, Hila Shinar, Salome Azoulay-Ginsburg, Ido Zemach, Gil Koren, Dganit Danino, Michael M. Kozlov, Roey J. Amir, Roy Beck

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Amphiphilic molecules and their self-assembled structures have long been the target of extensive research due to their potential applications in fields ranging from materials design to biomedical and cosmetic applications. Increasing demands for functional complexity have been met with challenges in biochemical engineering, driving researchers to innovate in the design of new amphiphiles. An emerging class of molecules, namely, peptide amphiphiles, combines key advantages and circumvents some of the disadvantages of conventional phospholipids and block copolymers. Herein, we present new peptide amphiphiles composed of an intrinsically disordered peptide conjugated to two variants of hydrophobic dendritic domains. These molecules, termed intrinsically disordered peptide amphiphiles (IDPA), exhibit a sharp pH-induced micellar phase-transition from low-dispersity spheres to extremely elongated worm-like micelles. We present an experimental characterization of the transition and propose a theoretical model to describe the pH-response. We also present the potential of the shape transition to serve as a mechanism for the design of a cargo hold-and-release application. Such amphiphilic systems demonstrate the power of tailoring the interactions between disordered peptides for various stimuli-responsive biomedical applications.

Original languageEnglish
Pages (from-to)11879-11888
Number of pages10
JournalJournal of the American Chemical Society
Issue number30
StatePublished - 4 Aug 2021
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2021 American Chemical Society.


We thank Diamond Light Source for time on Beamlines B21 (SM24693) and I22 (SM21971), Advanced Light Source for time on Beamline SIBYLS 12.3.1 (SB-00941), and the SOLEIL synchrotron facility for time on Beamline SWING (20170798). The work was supported by the Israel Science Foundation (grant numbers 1454/20, 1553/18, 3292/19, 1117/16), Deutsche Forschungsgemeinschaft through SFB 958, NWU-TAU nano center collaborative initiatives, the LMU-TAU collaboration initiatives, and DFG project GR1030/14-1. We thank Dr. Elvira Haimov and Dr. Boris Redko from the Blavatnik Center for Drug Discovery for their help with the synthesis and purification of the IDPAs. We also acknowledge fruitful discussions with Vladimir Uversky, Nathan Gianneschi, Joachim Rädler, Ram Avinery, and technical support of Mingming Zhang.

FundersFunder number
Deutsche ForschungsgemeinschaftSFB 958, GR1030/14-1
Israel Science Foundation1553/18, 1117/16, 3292/19, 1454/20


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