biostudies-literatureSapra KTSwiss National Science FoundationUnited States Department of Defense | United States Navy | ONR | Office of Naval Research Global6205https://www.ebi.ac.uk/biostudies/studies/S-EPMC7718915biostudies-literatureUnknown11(1)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.Nature communicationsNonlinear mechanics of lamin filaments and the meshwork topology build an emergent nuclear lamina.PMC7718915179418N00014-16-1-2333SNSF 31003A_179418Qin ZSapra KTDubrovsky-Gaupp AAebi UBuehler MJMedalia OMuller DJfalseNonlinear mechanics of lamin filaments and the meshwork topology build an emergent nuclear lamina.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.2020-01-01T00:00:00Z2020 Dec2024-11-14T13:43:33.36Z2021-02-21T04:33:54ZS-EPMC77189153327750210.1038/s41467-020-20049-8