Nucleation of protein mesocrystals via oriented attachment

Alexander E.S. Van Driessche, Nani Van Gerven, Rick R.M. Joosten, Wai Li Ling, Maria Bacia, Nico Sommerdijk, Mike Sleutel (Corresponding author)

Research output: Contribution to journalArticleAcademicpeer-review

23 Citations (Scopus)
48 Downloads (Pure)

Abstract

Self-assembly of proteins holds great promise for the bottom-up design and production of synthetic biomaterials. In conventional approaches, designer proteins are pre-programmed with specific recognition sites that drive the association process towards a desired organized state. Although proven effective, this approach poses restrictions on the complexity and material properties of the end-state. An alternative, hierarchical approach that has found wide adoption for inorganic systems, relies on the production of crystalline nanoparticles that become the building blocks of a next-level assembly process driven by oriented attachment (OA). As it stands, OA has not yet been observed for protein systems. Here we employ cryo-transmission electron microscopy (cryoEM) in the high nucleation rate limit of protein crystals and map the self-assembly route at molecular resolution. We observe the initial formation of facetted nanocrystals that merge lattices by means of OA alignment well before contact is made, satisfying non-trivial symmetry rules in the process. As these nanocrystalline assemblies grow larger we witness imperfect docking events leading to oriented aggregation into mesocrystalline assemblies. These observations highlight the underappreciated role of the interaction between crystalline nuclei, and the impact of OA on the crystallization process of proteins.

Original languageEnglish
Article number3902
Number of pages8
JournalNature Communications
Volume12
Issue number1
DOIs
Publication statusPublished - 23 Jun 2021

Bibliographical note

Funding Information:
We thank Dr. Guy Schoehn for his indispensable support with cryoEM data collection and insightful discussions. M.S. acknowledges financial support by the FWO under projects G0H5316N and 1516215N. This work used the platforms of the Grenoble Instruct-ERIC center (ISBG; UAR 3518 CNRS-CEA-UGA-EMBL) within the Grenoble Partnership for Structural Biology (PSB), supported by FRISBI (ANR-10-INBS-0005-02) and GRAL, financed within the University Grenoble Alpes graduate school (Ecoles Universitaires de Recherche) CBH-EUR-GS (ANR-17-EURE-0003). The electron microscope facility is supported by the Auvergne-Rhône-Alpes Region, the Fondation Recherche Medicale (FRM), the fonds FEDER and the GIS-Infrastructures en Biologie Sante et Agronomie (IBiSA). IBS acknowledges integration into the Interdisciplinary Research Institute of Grenoble (IRIG, CEA).

Publisher Copyright:
© 2021, The Author(s).

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