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Penn researchers show nuclear stiffness keeps stem cells and cancer cells in place
Date:2/25/2014

th lead author Takamasa Harada, a graduate student in his lab, conducted the studies with fellow lab members Joe Swift, Jerome Irianto, Jae-Won Shin, Kyle Spinler, Avathamsa Athirasala, Dave Dingal and Irena Ivanovska, as well as undergraduate student Rocky Diegmiller.

The study's experiments were conducted on immortalized human cancer cells as well as human-donor-derived mesenchymal stem cells, which are in wide use in clinical trials for tissue repair. The researchers either inhibited or overexpressed lamin-A in the cells, then placed both kinds on top of a thin sheet with very small pores. By adding blood serum to a chamber on the bottom of the porous sheet, the researchers encouraged the cells to push, pull and squeeze their nuclei through the pores.

Looking under a microscope at the cells that made it though the sheet revealed very few of the cells where lamin-A had been overexpressed. There was also a dearth of cells where lamin-A was strongly repressed. The cells that were most successful in migrating through the sheet's pores were the ones with lamin-A only slightly less than normal.

"The decreased migration with very low lamin-A levels was especially surprising," Harada said, "and so we measured the physical stiffness of the various nuclei, confirming that cell nuclei were systematically softer with low levels of lamin-A."

"While cells with stiffer nuclei are clearly unable to push or pull their nuclei through the pores," he said, "all of the softer nuclei could be moved through more easily, which presented a paradox."

To resolve the paradoxical decrease in cell number with very soft nuclei, the researchers saw that the cells on the bottom of the porous sheet turned on a marker for cell death that was otherwise absent from cells on top and the lower the lamin-A the greater the number of dying cells. As a cell squeezes its nucleus through a small pore, cell death is triggered and more so when lamin-A is low. '/>"/>

Contact: Evan Lerner
elerner@upenn.edu
215-573-6604
University of Pennsylvania
Source:Eurekalert  

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