Micro-Scale Topography Triggers Dynamic 3D Nuclear Deformations.

Area of Science:

• Cell biology
• Biophysics
• Mechanobiology

Background:

• Cell and nuclear deformation are crucial for navigating complex environments.
• Existing in vitro models do not fully replicate the confinement experienced by endothelial and epithelial cells.
• Basement membrane topography significantly influences nuclear deformation in tissue-lining cells.

Purpose of the Study:

• To investigate nuclear deformation in endothelial cells and myoblasts on microgroove substrates mimicking basement membrane topography.
• To analyze the forces driving nuclear penetration into microgrooves.
• To explore the potential of microgroove substrates for diagnosing nuclear mechanics-related pathologies.

Main Methods:

• Culturing endothelial cells and myoblasts on microgroove substrates.
• Utilizing atomic force microscopy to measure perinuclear stiffness.
• Observing nuclear deformation dynamics using microscopy.
• Analyzing myoblasts from laminopathy patients.

Main Results:

• Cells cultured on microgrooves exhibited large-scale 3D nuclear deformations, including nuclear penetration into grooves.
• Nuclear deformations were dynamic, with cyclic entry and exit from grooves, and did not cause significant DNA damage.
• Perinuclear stiffness transiently changed during deformation cycles.
• Cell-substrate adhesion stresses, rather than cytoskeleton forces, primarily drove nuclear penetration.
• Myoblasts from laminopathy patients showed abnormal nuclear deformations on microgrooves.

Conclusions:

• Microgroove substrates effectively mimic basement membrane topography, inducing realistic nuclear deformations in cells.
• Nuclear deformation in this context is primarily driven by cell adhesion and is dynamically regulated.
• Microgroove platforms show promise as a novel diagnostic tool for diseases involving aberrant nuclear mechanics, such as laminopathies.