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Nucleus. 2017 Sep 3;8(5):534-547. doi: 10.1080/19491034.2017.1322237. Epub 2017 Jun 22.

The nesprin-cytoskeleton interface probed directly on single nuclei is a mechanically rich system.

Author information

a Department of Biomedical Engineering , Vanderbilt University , Nashville , TN , USA.
b Department of Chemical and Biomolecular Engineering , Vanderbilt University , Nashville , TN , USA.
c Department of Mechanical Engineering , Korea Advanced Institute of Science and Technology , Daejeon , Korea.
d Instituto de Biologia Molecular y Celular del Cancer, Consejo Superior de Investigaciones Cientificas , University of Salamanca , Salamanca , Spain.
e Netherlands Cancer Institute , Amsterdam , The Netherlands.
f Division of Cardiovascular Medicine, Department of Medicine , Vanderbilt University Medical Center , Nashville , TN , USA.
g Severance Biomedical Science Institute, College of Medicine , Yonsei University , Seoul , Republic of Korea.
h Department of Molecular Physiology and Biophysics , Vanderbilt University Medical Center , Nashville , TN , USA.
i SMART-BioSystems and Micromechanics , National University of Singapore , Singapore.


The cytoskeleton provides structure and plays an important role in cellular function such as migration, resisting compression forces, and transport. The cytoskeleton also reacts to physical cues such as fluid shear stress or extracellular matrix remodeling by reorganizing filament associations, most commonly focal adhesions and cell-cell cadherin junctions. These mechanical stimuli can result in genome-level changes, and the physical connection of the cytoskeleton to the nucleus provides an optimal conduit for signal transduction by interfacing with nuclear envelope proteins, called nesprins, within the LINC (linker of the nucleus to the cytoskeleton) complex. Using single-molecule on single nuclei assays, we report that the interactions between the nucleus and the cytoskeleton, thought to be nesprin-cytoskeleton interactions, are highly sensitive to force magnitude and direction depending on whether cells are historically interfaced with the matrix or with cell aggregates. Application of ∼10-30 pN forces to these nesprin linkages yielded structural transitions, with a base transition size of 5-6 nm, which are speculated to be associated with partial unfoldings of the spectrin domains of the nesprins and/or structural changes of histones within the nucleus.


biomechanics; cytoskeleton; nesprin; nucleus; single molecule

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