Atomic Force Microscopy micro-rheology reveals large structural inhomogeneities in single cell-nuclei

Area of Science:

• Cell biology
• Biophysics
• Mechanobiology

Background:

• Cellular processes like growth, differentiation, and migration involve nuclear shape changes due to mechanical forces.
• Mechanical signals influence gene expression, but the mechanism of force transduction through the nucleus is not fully understood.

Purpose of the Study:

• To investigate how mechanical forces are transmitted through the nucleus.
• To quantitatively measure the mechanical properties (compliance) of individual mammalian cell nuclei.

Main Methods:

• Applied oscillatory mechanical strains (1-700 Hz) to individual nuclei from multiple mammalian cell lines.
• Compressed nuclei between two plates to measure their quantitative and qualitative mechanical responses.

Main Results:

• Nuclear compliance varied significantly (over one order of magnitude) and scaled with nuclear size.
• A consistent qualitative behavior was observed across cell lines: nuclei exhibited a softer, more viscous response at their periphery.
• This peripheral softness suggests reduced chromatin crosslinking in this region.

Conclusions:

• The nucleus's mechanical properties, particularly its peripheral softness, may play a crucial role in regulating gene transcription.
• This finding highlights the importance of mechano-transduction in the dynamic and active regions of the nucleus.