“The discovery that nuclei deform like droplets requires a fresh look at how nuclei shape can become abnormal in diseases such as cancer,” said Tanmay Lele, Ph.D., Unocal Professor of Biomedical Engineering. said.

Lele, a fellow at the Cancer Prevention Research Institute of Texas (CPRIT), co-led a team that uncovered the surprising mechanical behavior of the nucleus. Their findings were advanced science June 2022.

The genetic material that governs cell function and behavior, called the genome, is safely stored within the nucleus. Nearly 150 years of microscopy experience has taught pathologists and researchers that abnormalities in nuclear morphology are indicative of diseases such as cancer. Cancer cells with such abnormal nuclei can move to other parts of the body in a process called metastasis, where they can spread deadly.

Nucleus shape observation is still used in cancer diagnosis. However, it remains unclear why the nucleus becomes abnormal. Understanding how the nucleus deforms may help reveal ways to help the cell nucleus regain its normal shape and lead to new approaches to treating cancer.

Findings from this study are important in understanding how the protective layer surrounding the nucleus, called the lamina, helps maintain the shape of the nucleus.

Lele and his fellow researchers transformed fibroblasts, the most common type of connective tissue cells in animals, into miniature obstacle courses of tiny, flexible pillars one-hundredth the width of a human hair. We started investigating the behavior of the nuclei by placing them in In order for cells to crawl through this obstacle course, nuclei had to be squeezed between the pillars. The researchers observed the movement with an advanced high-resolution microscope that can image his 3D shape of the nucleus.

Imaging revealed that the pillars created deep depressions on the nuclear surface. Still, the overall shape of the nucleus was preserved, and the nucleus was able to pass through obstacles successfully like a droplet, unlike elastic rubber spheres that are elastic.

The study also revealed that depletion of lamin A/C, one of the normal protein components of the lamina, causes the nucleus to become entangled in obstacles. This finding suggests that Lamin A/C helps maintain the surface tension of the ‘nuclear droplets’.

“Our study demonstrates the underlying mechanisms by which the nucleus maintains its shape and protects its genome,” Lele said. “Our findings also help us better understand how malformed nuclei develop in cancer and how to restore them to normal. We are studying the implications of the drop model for the shape of the nucleus.”

This work was funded by a grant from the National Cancer Institute’s Physical Sciences-Oncology Network to Lele and additional support from the National Science Foundation to Co-Principal Investigator Richard B. Dickinson, Ph.D., Professor of Chemical Engineering. is financially supported by at the University of Florida. This research is funded in part by a CPRIT-established Investigator Award to Lele, facilitated through the Texas A&M Engineering Experiment Station.

In addition to Lele and Dickinson, principal investigators and researchers on this project include Drs. Pushkar P. Lele, Cynthia A. Reinhart-King, Kyle J. Roux, and Nathan J. Sniadecki. Students include Aditya Katiyar (first author of the paper), Jian Zhang, Jyot D. Antani, Yifan Yu, and Kelsey L. Scott.

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Materials provided Texas A&M UniversityOriginally written by Nancy Luedke. Note: Content may be edited for style and length.