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Design of biologically active binary protein 2D materials

Author

Listed:
  • Ariel J. Ben-Sasson

    (University of Washington
    University of Washington)

  • Joseph L. Watson

    (MRC Laboratory of Molecular Biology)

  • William Sheffler

    (University of Washington
    University of Washington)

  • Matthew Camp Johnson

    (University of Washington)

  • Alice Bittleston

    (MRC Laboratory of Molecular Biology)

  • Logeshwaran Somasundaram

    (University of Washington, School of Medicine)

  • Justin Decarreau

    (University of Washington
    University of Washington)

  • Fang Jiao

    (Pacific Northwest National Laboratory)

  • Jiajun Chen

    (University of Washington
    Pacific Northwest National Laboratory)

  • Ioanna Mela

    (University of Cambridge)

  • Andrew A. Drabek

    (Harvard Medical School)

  • Sanchez M. Jarrett

    (Harvard Medical School)

  • Stephen C. Blacklow

    (Harvard Medical School
    Dana-Farber Cancer Institute)

  • Clemens F. Kaminski

    (University of Cambridge)

  • Greg L. Hura

    (Lawrence Berkeley National Laboratory)

  • James J. Yoreo

    (University of Washington
    Pacific Northwest National Laboratory)

  • Justin M. Kollman

    (University of Washington)

  • Hannele Ruohola-Baker

    (University of Washington
    University of Washington, School of Medicine)

  • Emmanuel Derivery

    (MRC Laboratory of Molecular Biology)

  • David Baker

    (University of Washington
    University of Washington
    University of Washington)

Abstract

Ordered two-dimensional arrays such as S-layers1,2 and designed analogues3–5 have intrigued bioengineers6,7, but with the exception of a single lattice formed with flexible linkers8, they are constituted from just one protein component. Materials composed of two components have considerable potential advantages for modulating assembly dynamics and incorporating more complex functionality9–12. Here we describe a computational method to generate co-assembling binary layers by designing rigid interfaces between pairs of dihedral protein building blocks, and use it to design a p6m lattice. The designed array components are soluble at millimolar concentrations, but when combined at nanomolar concentrations, they rapidly assemble into nearly crystalline micrometre-scale arrays nearly identical to the computational design model in vitro and in cells without the need for a two-dimensional support. Because the material is designed from the ground up, the components can be readily functionalized and their symmetry reconfigured, enabling formation of ligand arrays with distinguishable surfaces, which we demonstrate can drive extensive receptor clustering, downstream protein recruitment and signalling. Using atomic force microscopy on supported bilayers and quantitative microscopy on living cells, we show that arrays assembled on membranes have component stoichiometry and structure similar to arrays formed in vitro, and that our material can therefore impose order onto fundamentally disordered substrates such as cell membranes. In contrast to previously characterized cell surface receptor binding assemblies such as antibodies and nanocages, which are rapidly endocytosed, we find that large arrays assembled at the cell surface suppress endocytosis in a tunable manner, with potential therapeutic relevance for extending receptor engagement and immune evasion. Our work provides a foundation for a synthetic cell biology in which multi-protein macroscale materials are designed to modulate cell responses and reshape synthetic and living systems.

Suggested Citation

  • Ariel J. Ben-Sasson & Joseph L. Watson & William Sheffler & Matthew Camp Johnson & Alice Bittleston & Logeshwaran Somasundaram & Justin Decarreau & Fang Jiao & Jiajun Chen & Ioanna Mela & Andrew A. Dr, 2021. "Design of biologically active binary protein 2D materials," Nature, Nature, vol. 589(7842), pages 468-473, January.
  • Handle: RePEc:nat:nature:v:589:y:2021:i:7842:d:10.1038_s41586-020-03120-8
    DOI: 10.1038/s41586-020-03120-8
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    Cited by:

    1. Matthew Herdman & Buse Isbilir & Andriko Kügelgen & Ulrike Schulze & Alan Wainman & Tanmay A. M. Bharat, 2024. "Cell cycle dependent coordination of surface layer biogenesis in Caulobacter crescentus," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Sanahan Vijayakumar & Robert G. Alberstein & Zhiyin Zhang & Yi-Sheng Lu & Adriano Chan & Charlotte E. Wahl & James S. Ha & Deborah E. Hunka & Gerry R. Boss & Michael J. Sailor & F. Akif Tezcan, 2024. "Designed 2D protein crystals as dynamic molecular gatekeepers for a solid-state device," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    3. Yihong Zhong & Lijia Xu & Chen Yang & Le Xu & Guyu Wang & Yuna Guo & Songtao Cheng & Xiao Tian & Changjiang Wang & Ran Xie & Xiaojian Wang & Lin Ding & Huangxian Ju, 2023. "Site-selected in situ polymerization for living cell surface engineering," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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