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Nuclear constriction segregates mobile nuclear proteins away from chromatin
Jerome Irianto1,2, Charlotte R Pfeifer1,2,3, Rachel R Bennett1,3
1Physical Sciences Oncology Center at Penn, University of Pennsylvania, Philadelphia, PA 19104.
Molecular Biology of the Cell
|November 1, 2016
Summary
Cancer cell nuclei compact during migration, increasing chromatin density and depleting mobile nuclear factors like DNA repair proteins. This physical change can delay DNA damage responses.
Area of Science:
- Cell biology
- Biophysics
- Cancer research
Background:
- Cellular migration involves navigating physical barriers, potentially altering nuclear structure.
- Chromatin organization and nuclear factor mobility are crucial for DNA repair and gene regulation.
Purpose of the Study:
- To investigate the physical effects of cellular constriction on nuclear chromatin density and mobile nuclear factors.
- To understand the functional consequences of these nuclear changes during cancer cell migration.
Main Methods:
- Observing cancer cell migration through rigid micropores and passive pulling into micropipettes.
- Quantifying chromatin compaction using DNA and histone intensity measurements.
- Assessing mobile nuclear factor depletion via fluorescence microscopy.
Main Results:
- Local chromatin compaction increases to nearly 100% volume fraction within constrictions.
- Mobile nuclear proteins, including DNA repair factors, are depleted to near 0% within constrictions.
- Constricted migration delays DNA damage responses, as shown in studies with a specific nuclease.
Conclusions:
- Cellular squeezing through constrictions causes significant nuclear physical changes: chromatin compaction and mobile factor depletion.
- These physical perturbations can impact essential nuclear functions, such as DNA damage repair.
- Understanding these mechanisms is vital for cancer cell invasion and therapeutic strategies.
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