Nuclear Deformation in Response to Mechanical Confinement is Cell Type Dependent

Area of Science:

• Cell biology
• Biophysics
• Mechanobiology

Background:

• Cellular mechanosensing is crucial for regulating cell phenotype and function.
• The nucleus plays a key role in transmitting mechanical forces to the cell.
• Understanding nuclear deformation is vital for comprehending cell behavior in confined environments.

Purpose of the Study:

• To investigate how mechanical confinement affects nuclear deformation in various cell types.
• To determine the role of cytoskeletal elements in controlling nuclear deformation.
• To compare nuclear mechanics across human cancer cells, mesenchymal stem cells, and mouse fibroblasts.

Main Methods:

• Cells (MDA-MB-231, MSCs, L929) were cultured in microfluidic devices with varying channel sizes.
• Nuclear morphology and volume were quantified using image processing of fluorescently labeled nuclei.
• Cytoskeletal elements (microtubules, myosin II) were inhibited to assess their role in nuclear deformation.

Main Results:

• Nuclear deformation varied by cell type under increasing confinement.
• L929 cells showed increased nuclear length and decreased volume with confinement; MSCs showed decreased volume.
• Cytoskeletal inhibition affected nuclear deformation primarily in MSCs in wider channels.

Conclusions:

• Nuclear deformation responses to mechanical confinement differ significantly across cell types.
• The cytoskeleton plays distinct roles in regulating nuclear mechanics depending on the cell type and channel geometry.
• Findings provide insights into nuclear mechanics in physiologically relevant confined spaces.