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

Area of Science:

• Cell Biology
• Biophysics
• Mechanobiology

Background:

• The cytoskeleton provides cellular structure and regulates functions like migration and transport.
• Mechanical stimuli, such as fluid shear stress, can alter cytoskeleton organization and lead to genome-level changes.
• The LINC complex, involving nesprins, physically connects the cytoskeleton to the nucleus, facilitating signal transduction.

Purpose of the Study:

• To investigate the force-dependent nature of nesprin-cytoskeleton interactions.
• To determine how these interactions differ based on cellular environment (matrix vs. cell aggregates).
• To characterize structural transitions within the LINC complex under applied forces.

Main Methods:

• Single-molecule on single nuclei assays were employed.
• Controlled forces (∼10-30 pN) were applied to nesprin linkages.
• Structural transitions were measured using nanometer precision.

Main Results:

• Nesprin-cytoskeleton interactions are highly sensitive to force magnitude and direction.
• These interactions vary depending on whether cells are interfaced with the extracellular matrix or with cell aggregates.
• Applied forces induced structural transitions in nesprin linkages, with a base transition size of 5-6 nm.

Conclusions:

• The study reveals the mechanosensitive nature of the LINC complex and its role in transmitting physical cues to the nucleus.
• Structural transitions observed are potentially linked to spectrin domain unfolding in nesprins or histone modifications.
• These findings highlight a mechanism for how mechanical forces can influence nuclear structure and function.