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Nuclear Migration in the Drosophila Oocyte
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Nuclear plasticity increases susceptibility to damage during confined migration
Abhishek Mukherjee1,2,3, Amlan Barai4, Ramesh K Singh2
1IITB-Monash Research Academy, IIT Bombay, Mumbai, India.
Plos Computational Biology
|October 9, 2020
Summary
Cell nuclei deform during migration, potentially causing damage. Nuclear softening aids migration and reduces DNA damage, while stiffening causes damage through plastic deformation.
Area of Science:
- Cell biology
- Biophysics
- Mechanobiology
Background:
- Large nuclear deformations during confined cell migration are linked to nuclear membrane rupture and DNA damage.
- The precise stresses driving nuclear damage during migration are not fully understood.
Purpose of the Study:
- To model the evolution of nuclear shape and stresses during confined cell migration.
- To investigate the relationship between nuclear mechanical properties, migration, and DNA damage.
Main Methods:
- Quasi-static plane strain finite element modeling of cell migration through a deformable matrix.
- Transwell migration experiments using fibrosarcoma cells with varying nuclear stiffness.
Main Results:
- Finite element models predicted that plastic deformation of stiff nuclei in stiffer matrices reduced nuclear stress but caused membrane kinking.
- Experimental results showed that nuclear softening increased cell invasiveness.
- Nuclear stiffening led to plastic deformation and increased DNA damage.
Conclusions:
- Nuclear softening is advantageous for cell migration through confined spaces.
- Plastic deformation of the nucleus during migration through stiff tissues can induce nuclear membrane disruption and DNA damage.
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