Biomolecular condensates formed by designer minimalistic peptides

Avigail Baruch Leshem, Sian Sloan-Dennison, Tlalit Massarano, Shavit Ben-David, Duncan Graham, Karen Faulds, Hugo E. Gottlieb, Jordan H. Chill, Ayala Lampel

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

Inspired by the role of intracellular liquid-liquid phase separation (LLPS) in formation of membraneless organelles, there is great interest in developing dynamic compartments formed by LLPS of intrinsically disordered proteins (IDPs) or short peptides. However, the molecular mechanisms underlying the formation of biomolecular condensates have not been fully elucidated, rendering on-demand design of synthetic condensates with tailored physico-chemical functionalities a significant challenge. To address this need, here we design a library of LLPS-promoting peptide building blocks composed of various assembly domains. We show that the LLPS propensity, dynamics, and encapsulation efficiency of compartments can be tuned by changes to the peptide composition. Specifically, with the aid of Raman and NMR spectroscopy, we show that interactions between arginine and aromatic amino acids underlie droplet formation, and that both intra- and intermolecular interactions dictate droplet dynamics. The resulting sequence-structure-function correlation could support the future development of compartments for a variety of applications.

Original languageEnglish
Article number421
JournalNature Communications
Volume14
Issue number1
DOIs
StatePublished - 26 Jan 2023

Bibliographical note

Publisher Copyright:
© 2023, The Author(s).

Funding

This research was supported by the Israel Science Foundation, Grant No. 2589/21 (A.L.). We thank Dr. M. Afri for help with NMR experiments and analysis. T.M. thanks the ADAMA Center for Novel Delivery Systems in Crop Protection for the PhD ADAMA Fellowship and the Marian Gertner Institute for Medical Nano systems for the Gertner scholarship.

FundersFunder number
ADAMA Center for Novel Delivery Systems
Israel Science Foundation2589/21

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