Isolated nuclei stiffen in response to low intensity vibration

Area of Science:

• Cellular Mechanics
• Biophysics
• Stem Cell Biology

Background:

• The nucleus is a critical cellular component that senses and responds to mechanical stimuli through direct input and molecular transducers.
• While isolated nuclei show force adaptation ex vivo, mechanisms of nuclear mechanoadaptation to physiological forces in vivo are not well understood.
• Mesenchymal stem cells (MSCs) are known to respond to mechanical cues, but nuclear responses require further investigation.

Purpose of the Study:

• To investigate nuclear mechanoadaptation in live cells using an atomic force microscopy (AFM) approach.
• To determine if nuclear stiffness increases following low intensity vibration (LIV) in MSCs.
• To elucidate the molecular mechanisms underlying LIV-induced nuclear stiffening.

Main Methods:

• Developed an AFM-based procedure to probe live nuclei isolated from MSCs.
• Applied low intensity vibration (LIV) to MSCs under controlled conditions (0.7 g, 90 Hz, 20 min, 4x with 1h intervals).
• Assessed nuclear stiffness, Linker of Nucleoskeleton and Cytoskeleton (LINC) complex function, and heterochromatin structure.

Main Results:

• Isolated nuclei were 30% softer than nuclei within intact MSCs before LIV.
• LIV treatment increased isolated nucleus stiffness by 75% compared to controls.
• LIV-induced nuclear stiffening depended on a functional LINC complex but not on increased LaminA/C or Sun-2 levels.
• LIV decreased the heterochromatin to nuclear area ratio by 25%, indicating altered heterochromatin structure.

Conclusions:

• Increased cell stiffness in MSCs subjected to LIV is partly due to enhanced nuclear stiffness.
• LIV induces nuclear stiffening and alters heterochromatin structure, requiring a functional LINC complex.
• These findings highlight the nucleus's role in cellular mechanotransduction and adaptation to mechanical challenges.