The effect of the LINC Complex on the nanomechanics of individual live cells


Mechanical forces influence many aspects of cell behavior. Mechanotransduction is classically described as the process whereby forces acting on the cell surface are transduced into biochemical functions, eventually reaching the cell nucleus. While much has been studied about the role of focal adhesions and cytoskeletal actin to control cell mechanics, the role of the LINC complex, linking the Nucleoskeleton with the cytoskeleton, has remained elusive. Here we will employ a combination of cell biology, molecular biology and advanced high-resolution Atomic Force Microscopy to dissect the molecular determinants that govern the mechanical stability of individual cells and isolated nuclei.


Atilla-Gokcumen, Muro, E.; Relat-Goberna, J.; Sasse, S.; Bedigian, S.; Coughlin, M.L.; Garcia-Manyes, S.; Eggert, U.S.; «Dividing cells regulate their lipid composition and localization». Cell (2014), 156 (3), 428


Garcia-Manyes, S.; Dougan, L.; Badilla, C. L.; Brujic, J; Fernandez, J.M.; «Direct observation of an ensemble of stable collapsed states in the mechanical folding of ubiquitin», Proc. Natl. Acad. Sci. USA, (2009), 106 (26),10534-10539


Garcia-Manyes, S; Liang, J.; Szoszkiewicz, R.; Kuo, T.; Fernandez, J.M.; «Force-activated reactivity switch in a bimolecular chemical reaction», Nature Chemistry, (2009), 3, 236-242


Zhang Q, Bethmann C, Worth NF, Davies JD, Wasner C, Feuer A, Ragnauth CD, Yi Q, Mellad JA, Warren DT, Wheeler MA, Ellis JA, Skepper JN, Vorgerd M, Schlotter-Weigel B, Weissberg PL, Roberts RG, Wehnert M, Shanahan CM. (2007) Nesprin-1 and -2 are involved in the pathogenesis of Emery Dreifuss muscular dystrophy and are critical for nuclear envelope integrity. Hum Mol Genet. 16(23):2816-33.


Lombardi ML, Jaalouk DE, Shanahan CM, Burke B, Roux KJ, Lammerding J. (2011). The interaction between nesprins and sun proteins at the nuclear envelope is critical for force transmission between the nucleus and cytoskeleton. J Biol Chem. 29;286(30):26743-53.

Biological Areas:

Cell Biology
Chemical Biology


Molecules, cells and industrial biotechnology