Shape selection and mis-assembly in viral capsid formation by elastic frustration

  1. Carlos I Mendoza  Is a corresponding author
  2. David Reguera
  1. National Autonomous University of Mexico, Mexico
  2. Universitat de Barcelona, Spain

Abstract

The successful assembly of a closed protein shell (or capsid) is a key step in the replication of viruses and in the production of artificial viral cages for bio/nanotechnological applications. During self-assembly, the favorable binding energy competes with the energetic cost of the growing edge and the elastic stresses generated due to the curvature of the capsid. As a result, incomplete structures such as open caps, cylindrical or ribbon-shaped shells may emerge, preventing the successful replication of viruses. Using elasticity theory and coarse-grained simulations, we analyze the conditions required for these processes to occur and their significance for empty virus self-assembly. We find that the outcome of the assembly can be recast into a universal phase diagram showing that viruses with high mechanical resistance cannot be self-assembled directly as spherical structures. The results of our study justify the need of a maturation step and suggest promising routes to hinder viral infections by inducing mis-assembly.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Carlos I Mendoza

    Materials Research Institute, National Autonomous University of Mexico, Mexico City, Mexico
    For correspondence
    cmendoza@iim.unam.mx
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9769-240X
  2. David Reguera

    Departament de Física de la Materia Condensada, Universitat de Barcelona, Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6395-6112

Funding

Universidad Nacional Autónoma de México (DGAPA IN-110516)

  • Carlos I Mendoza

Universidad Nacional Autónoma de México (DGAPA IN-103419)

  • Carlos I Mendoza

Gobierno de Espana (FIS2015-67837-P)

  • David Reguera

MINECO/FEDER, UE (PGC2018-098373-B-I00)

  • David Reguera

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Pierre Sens, Institut Curie, PSL Research University, CNRS, France

Version history

  1. Received: October 7, 2019
  2. Accepted: April 6, 2020
  3. Accepted Manuscript published: April 21, 2020 (version 1)
  4. Version of Record published: April 24, 2020 (version 2)

Copyright

© 2020, Mendoza & Reguera

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 1,706
    Page views
  • 214
    Downloads
  • 13
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Carlos I Mendoza
  2. David Reguera
(2020)
Shape selection and mis-assembly in viral capsid formation by elastic frustration
eLife 9:e52525.
https://doi.org/10.7554/eLife.52525

Share this article

https://doi.org/10.7554/eLife.52525

Further reading

    1. Microbiology and Infectious Disease
    2. Physics of Living Systems
    Fabien Duveau, Céline Cordier ... Pascal Hersen
    Research Article

    Natural environments of living organisms are often dynamic and multifactorial, with multiple parameters fluctuating over time. To better understand how cells respond to dynamically interacting factors, we quantified the effects of dual fluctuations of osmotic stress and glucose deprivation on yeast cells using microfluidics and time-lapse microscopy. Strikingly, we observed that cell proliferation, survival, and signaling depend on the phasing of the two periodic stresses. Cells divided faster, survived longer, and showed decreased transcriptional response when fluctuations of hyperosmotic stress and glucose deprivation occurred in phase than when the two stresses occurred alternatively. Therefore, glucose availability regulates yeast responses to dynamic osmotic stress, showcasing the key role of metabolic fluctuations in cellular responses to dynamic stress. We also found that mutants with impaired osmotic stress response were better adapted to alternating stresses than wild-type cells, showing that genetic mechanisms of adaptation to a persistent stress factor can be detrimental under dynamically interacting conditions.

    1. Physics of Living Systems
    Josep-Maria Armengol-Collado, Livio Nicola Carenza, Luca Giomi
    Research Article Updated

    We formulate a hydrodynamic theory of confluent epithelia: i.e. monolayers of epithelial cells adhering to each other without gaps. Taking advantage of recent progresses toward establishing a general hydrodynamic theory of p-atic liquid crystals, we demonstrate that collectively migrating epithelia feature both nematic (i.e. p = 2) and hexatic (i.e. p = 6) orders, with the former being dominant at large and the latter at small length scales. Such a remarkable multiscale liquid crystal order leaves a distinct signature in the system’s structure factor, which exhibits two different power-law scaling regimes, reflecting both the hexagonal geometry of small cells clusters and the uniaxial structure of the global cellular flow. We support these analytical predictions with two different cell-resolved models of epithelia – i.e. the self-propelled Voronoi model and the multiphase field model – and highlight how momentum dissipation and noise influence the range of fluctuations at small length scales, thereby affecting the degree of cooperativity between cells. Our construction provides a theoretical framework to conceptualize the recent observation of multiscale order in layers of Madin–Darby canine kidney cells and pave the way for further theoretical developments.