The Structure and the Mechanical Properties of Nuclear Lamins

Shani Deri, Department of Chemical Engineering, SCE- Shamoon College of Engineering , Ashdod, Israel,
                     Department of Chemical Engineering, Ariel University, Ariel, Israel
Maayan Khayat, Department of Life Sciences and the National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva, Israel
David Wolf, Department of Chemical Engineering, Ariel University, Ariel, Israel
Yosef Gruenbaum, Department of Genetics, The Hebrew University of Jerusalem, Jerusalem, Israel
Ohad Medalia, Department of Life Sciences and the National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva, Israel
                           Department of Biochemistry, University of Zurich, Zurich, Switzerland
Kfir Ben-Harush, Department of Chemical Engineering, SCE- Shamoon College of Engineering , Ashdod, Israel

The nuclear lamina is a meshwork layer apposed to the inner nuclear membrane of all metazoan cell nuclei. It is composed mainly of nuclear lamins that classified as type V intermediate filament proteins. Besides providing mechanical support to the nucleus and maintaining nuclear shape, the lamina is involved in many nuclear activities, including chromatin organization, transcription and replication. Recent data suggests that tissue stiffness and stress increase lamin-A levels within the nucleus providing stabilized nucleus, thus, lamins play important role in tissue mechano-transduction. What are the structures that lamins form in different tissues and how this structural organization is relate to the mechanical properties is unknown. Much of the molecular information about lamins assembly comes from in-vitro structural analysis. Most lamins assemble in vitro into paracrystalline structures; though the formation of paracrystals within the nucleus has not been revealed, new study has shown that the organization of human A- and B- lamins into filamentous structure within the nucleus in-situ is similar to its organization into paracrystal. Here, assembly of B-type C. elegans lamins into macroscopic fibers through the formation of paracrystals revealed the mechanical properties of lamin assemblies. The relationship between structure and mechanics of lamin fibers has been investigated using cryo electron tomography and different lamin constructs that form altered paracrystal structures, namely lamins missing 'tail' or 'head' domains, and point mutation that cause severe diseases in human. The unique mechanical properties and behavior of lamin fibers revealed here can lead to new biomaterials in the field of tissue engineering, various medical applications and possibly a basic understanding of the mechanical properties of intracellular nanomaterials.