Nonlinear mechanics of lamin filaments and the meshwork topology build an emergent nuclear lamina

K. Tanuj Sapra, Zhao Qin, Anna Dubrovsky-Gaupp, Ueli Aebi, Daniel J. Müller, Markus J. Buehler, Ohad Medalia

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

The nuclear lamina—a meshwork of intermediate filaments termed lamins—is primarily responsible for the mechanical stability of the nucleus in multicellular organisms. However, structural-mechanical characterization of lamin filaments assembled in situ remains elusive. Here, we apply an integrative approach combining atomic force microscopy, cryo-electron tomography, network analysis, and molecular dynamics simulations to directly measure the mechanical response of single lamin filaments in three-dimensional meshwork. Endogenous lamin filaments portray non-Hookean behavior – they deform reversibly at a few hundred picoNewtons and stiffen at nanoNewton forces. The filaments are extensible, strong and tough similar to natural silk and superior to the synthetic polymer Kevlar®. Graph theory analysis shows that the lamin meshwork is not a random arrangement of filaments but exhibits small-world properties. Our results suggest that lamin filaments arrange to form an emergent meshwork whose topology dictates the mechanical properties of individual filaments. The quantitative insights imply a role of meshwork topology in laminopathies.

Original languageEnglish (US)
Article number6205
JournalNature Communications
Volume11
Issue number1
DOIs
StatePublished - Dec 2020

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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