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Cell migration through dense tissues or small capillaries can elongate the nucleus and even damage it, and any impact on cell cycle has the potential to affect various processes including carcinogenesis. Here, nuclear rupture and DNA damage increase with constricted migration in different phases of cell cycle-which we show is partially repressed. We study several cancer lines that are contact inhibited or not and that exhibit diverse frequencies of nuclear lamina rupture after migration through small pores. DNA repair factors invariably mislocalize after migration, and an excess of DNA damage is evident as pan-nucleoplasmic foci of phosphoactivated ATM and gamma H2AX. Foci counts are suppressed in late cell cycle as expected of mitotic checkpoints, and migration of contact-inhibited cells through large pores into sparse microenvironments leads also as expected to cell-cycle reentry and no effect on a basal level of damage foci. Constricting pores delay such reentry while excess foci occur independent of cell-cycle phase. Knockdown of repair factors increases DNA damage independent of cell cycle, consistent with effects of constricted migration. Because such migration causes DNA damage and impedes proliferation, it illustrates a cancer cell fate choice of "go or grow."
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This content will become publicly available on March 28, 2026
Excess surface area of the nuclear lamina enables unhindered cell migration through constrictions
Cell migration through narrow spaces is essential in wound healing and metastatic spread of cancer. Cells must deform the large nucleus to fit through constricting channels. To understand the role of the nuclear lamina in limiting cell migration through constrictions, we imaged it in cells migrating through periodic constricting channels in a microdevice. The lamina underwent cycles of wrinkling and smoothing as the nucleus changed from an irregular, rounded shape in the wide channel regions between constrictions to a smooth, hourglass shape as the nucleus passed through the center of a constriction. The laminar surface area of nuclei within constrictions was measured to be at or above the computationally predicted threshold area for the nuclear volume. The channels excluded control nuclei that had insufficient excess surface area, but not nuclei lacking lamin A/C. Thus, the excess surface area of the nuclear lamina enables cell migration through constricting channels.
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- PAR ID:
- 10598372
- Publisher / Repository:
- American Association for the Advancement of Science
- Date Published:
- Journal Name:
- Science Advances
- Volume:
- 11
- Issue:
- 13
- ISSN:
- 2375-2548
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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