The molecular architecture of lamins in somatic cells.

The nuclear lamina is a fundamental constituent of metazoan nuclei. It is composed mainly of lamins, which are intermediate filament proteins that assemble into a filamentous meshwork, bridging the nuclear envelope and chromatin. Besides providing structural stability to the nucleus, the lamina is involved in many nuclear activities, including chromatin organization, transcription and replication. However, the structural organization of the nuclear lamina is poorly understood. Here we use cryo-electron tomography to obtain a detailed view of the organization of the lamin meshwork within the lamina. Data analysis of individual lamin filaments resolves a globular-decorated fibre appearance and shows that A- and B-type lamins assemble into tetrameric filaments of 3.5 nm thickness. Thus, lamins exhibit a structure that is remarkably different from the other canonical cytoskeletal elements. Our findings define the architecture of the nuclear lamin meshworks at molecular resolution, providing insights into their role in scaffolding the nuclear lamina.

Biomimetic nuclear lamin fibers with remarkable toughness and stiffness.

The native hagfish slime threads, which are made up of two intermediate filament (IF)-like proteins, exhibit mechanical properties comparable to dragline spider silk fiber, the toughest fiber in nature. However, unlike silk, the design of artificial IF-protein-based fibers has been rarely studied, possibly because the unique hierarchical organization of the keratin-like proteins within these threads is challenging to mimic, and consequently, extraordinary fiber mechanics has not been shown in slime threads from recombinant IF-protein-based system. Here, we have reported the synthesis and properties of recombinant type V IF-protein, based on the Caenorhabditis elegans (Ce) lamin gene. The protein was solubilized and wet-spun into aqueous solutions to prepare Ce-lamin fibers by varying injection flow rates and Ca+2 ion concentrations in the coagulation buffer. At specific set of conditions, Ce-lamin fibers demonstrated remarkable toughness and stiffness, comparable to hagfish slime threads and natural dragline spider silk. Transmission electron microscopy analysis showed that paracrystals were the main nanometric structure within the fibers. This study demonstrates that outstanding mechanical properties can be achieved with recombinant IF-proteins through self-organization. Thus, these results have broadened the pool of fibrous proteins that can be used in functional materials for a diverse range of applications.

The assembly of C. elegans lamins into macroscopic fibers.

Intermediate filament (IF) proteins are known mainly by their propensity to form viscoelastic filamentous networks within cells. In addition, IF-proteins are essential parts of various biological materials, such as horn and hagfish slime threads, which exhibit a range of mechanical properties from hard to elastic. These properties and their self-assembly nature made IF-proteins attractive building blocks for biomimetic and biological materials in diverse applications. Here we show that a type V IF-protein, the Caenorhabditis elegans nuclear lamin (Ce-lamin), is a promising building block for protein-based fibers. Electron cryo-tomography of vitrified sections enabled us to depict the higher ordered assembly of the Ce-lamin into macroscopic fibers through the creation of paracrystalline fibers, which are prominent in vitro structures of lamins. The lamin fibers respond to tensile force as other IF-protein-based fibers, i.e., hagfish slime threads, and possess unique mechanical properties that may potentially be used in certain applications. The self-assembly nature of lamin proteins into a filamentous structure, which is further assembled into a complex network, can be easily modulated. This knowledge may lead to a better understanding of the relationship in IF-proteins-based fibers and materials, between their hierarchical structures and their mechanical properties.