Microtubules soften due to cross-sectional flattening

  1. Edvin Memet
  2. Feodor Hilitsk
  3. Margaret A Morris
  4. Walter J Schwenger
  5. Zvonimir Dogic
  6. L Mahadevan  Is a corresponding author
  1. Harvard University, United States
  2. Brandeis University, United States
  3. University of California, Santa Barbara, United States

Abstract

We use optical trapping to continuously bend an isolated microtubule while simultaneously measuring the applied force and the resulting filament strain, thus allowing us to determine its elastic properties over a wide range of applied strains. We find that, while in the low-strain regime, microtubules may be quantitatively described in terms of the classical Euler-Bernoulli elastic filament, above a critical strain they deviate from this simple elastic model, showing a softening response with increasing deformations. A three-dimensional thin-shell model, in which the increased mechanical compliance is caused by flattening and eventual buckling of the filament cross-section, captures this softening effect in the high strain regime and yields quantitative values of the effective mechanical properties of microtubules. Our results demonstrate that properties of microtubules are highly dependent on the magnitude of the applied strain and offer a new interpretation for the large variety in microtubule mechanical data measured by different methods.

Data availability

Source data has been provided for Figure 6 along with source code files. Source code files have been provided for Figure 2 along with instructions for generating the data.

The following previously published data sets were used

Article and author information

Author details

  1. Edvin Memet

    Department of Physics, Harvard University, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9414-597X
  2. Feodor Hilitsk

    Department of Physics, Brandeis University, Waltham, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5629-1407
  3. Margaret A Morris

    Department of Physics, Brandeis University, Waltham, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Walter J Schwenger

    Department of Physics, Brandeis University, Waltham, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Zvonimir Dogic

    Department of Physics, University of California, Santa Barbara, Santa Barbara, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. L Mahadevan

    Department of Physics, Harvard University, Cambridge, United States
    For correspondence
    lm@seas.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5114-0519

Funding

U.S. Department of Energy (DE-SC0010432TDD)

  • Feodor Hilitsk
  • Zvonimir Dogic

National Science Foundation (NSF-MCB-1329623)

  • Zvonimir Dogic

National Science Foundation (NSF- -CMMI-1068566)

  • Zvonimir Dogic

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

Reviewing Editor

  1. Manuel Thery, CEA, France

Version history

  1. Received: February 6, 2018
  2. Accepted: June 1, 2018
  3. Accepted Manuscript published: June 1, 2018 (version 1)
  4. Version of Record published: July 12, 2018 (version 2)
  5. Version of Record updated: February 28, 2019 (version 3)

Copyright

© 2018, Memet et al.

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

  • 4,465
    views
  • 517
    downloads
  • 34
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

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. Edvin Memet
  2. Feodor Hilitsk
  3. Margaret A Morris
  4. Walter J Schwenger
  5. Zvonimir Dogic
  6. L Mahadevan
(2018)
Microtubules soften due to cross-sectional flattening
eLife 7:e34695.
https://doi.org/10.7554/eLife.34695

Share this article

https://doi.org/10.7554/eLife.34695

Further reading

    1. Cell Biology
    Yoko Nakai-Futatsugi, Jianshi Jin ... Masayo Takahashi
    Research Article

    Retinal pigment epithelium (RPE) cells show heterogeneous levels of pigmentation when cultured in vitro. To know whether their color in appearance is correlated with the function of the RPE, we analyzed the color intensities of human-induced pluripotent stem cell-derived RPE cells (iPSC-RPE) together with the gene expression profile at the single-cell level. For this purpose, we utilized our recent invention, Automated Live imaging and cell Picking System (ALPS), which enabled photographing each cell before RNA-sequencing analysis to profile the gene expression of each cell. While our iPSC-RPE were categorized into four clusters by gene expression, the color intensity of iPSC-RPE did not project any specific gene expression profiles. We reasoned this by less correlation between the actual color and the gene expressions that directly define the level of pigmentation, from which we hypothesized the color of RPE cells may be a temporal condition not strongly indicating the functional characteristics of the RPE.

    1. Cancer Biology
    2. Cell Biology
    Savvas Nikolaou, Amelie Juin ... Laura M Machesky
    Research Article

    Pancreatic ductal adenocarcinoma carries a dismal prognosis, with high rates of metastasis and few treatment options. Hyperactivation of KRAS in almost all tumours drives RAC1 activation, conferring enhanced migratory and proliferative capacity as well as macropinocytosis. Macropinocytosis is well understood as a nutrient scavenging mechanism, but little is known about its functions in trafficking of signaling receptors. We find that CYRI-B is highly expressed in pancreatic tumours in a mouse model of KRAS and p53-driven pancreatic cancer. Deletion of Cyrib (the gene encoding CYRI-B protein) accelerates tumourigenesis, leading to enhanced ERK and JNK-induced proliferation in precancerous lesions, indicating a potential role as a buffer of RAC1 hyperactivation in early stages. However, as disease progresses, loss of CYRI-B inhibits metastasis. CYRI-B depleted tumour cells show reduced chemotactic responses to lysophosphatidic acid, a major driver of tumour spread, due to impaired macropinocytic uptake of the lysophosphatidic acid receptor-1. Overall, we implicate CYRI-B as a mediator of growth and signaling in pancreatic cancer, providing new insights into pathways controlling metastasis.