Nuclear deformability and telomere dynamics are regulated by cell geometric constraints

Area of Science:

• Cell Biology
• Biophysics
• Mechanobiology

Background:

• Cytoskeletal forces transmit to the nucleus via the nuclear envelope and lamin meshwork.
• While nuclear morphology changes are studied, the impact on nuclear and chromatin dynamics is less understood.

Purpose of the Study:

• Investigate how active cytoskeletal forces regulate nuclear deformability and chromatin dynamics.
• Explore the role of cell geometry in modulating these nuclear responses.

Main Methods:

• Utilized micropatterned substrates to create distinct cytoskeletal states in mouse fibroblasts.
• Manipulated cytoskeletal components (actin, myosin, formin) and lamin A/C levels.
• Tracked spatiotemporal dynamics of heterochromatin foci and telomeres.

Main Results:

• Constrained, isotropic cells exhibited more deformable nuclei compared to elongated, polarized cells.
• Nuclear deformability was sensitive to cytoskeletal perturbations and lamin A/C levels.
• Constrained geometry led to increased heterochromatin and telomere dynamics.
• Chromatin dynamics showed inherent structural memory upon recovery from actin depolymerization.

Conclusions:

• Active cytoskeletal forces and lamin A/C nucleoskeleton rigidity jointly regulate nuclear and chromatin dynamics.
• Cell geometric constraints are critical regulators of chromatin remodeling, genome integrity, and cell migration.