Researchers develop new tools to explore mechanobiology of cell nucleus

A team of researchers led by UF Health Cancer Center member Xin Tang, Ph.D., assistant professor in the department of mechanical & aerospace engineering, has developed a new biophysics technique to shed light on the mechanobiology of the nucleus in single cancer and normal cells.

The researchers designed, fabricated and implemented a new magnetic force actuator that applies precise and noninvasive 3D mechanical stimuli to directly deform the cell nucleus. Using CRISPR/Cas9-engineered cells, the team demonstrated that this tool, combined with high-resolution confocal and super-resolution fluorescent imaging, shows the real-time dynamics of a mechano-sensitive yes-associated protein (YAP) in single cells as a function of nucleus deformation.

The findings were published recently in the Journal of Visualized Experiments.

This work is expected to play an important role in explaining how the cell nucleus senses, transduces and responds to mechanical stimuli. It was previously difficult to access and quantify nucleus mechanics with conventional tools, resulting in a gap in knowledge on the relationship between nucleus mechanotransduction and cell function.

These noninvasive tools pave the way for direct and researcher-programmed epigenetic manipulation of the individual nucleus and other organelles in single cells, said Tang, who is also an affiliate faculty member in the J. Crayton Pruitt Family department of biomedical engineering. These new methodologies will enable researchers to elucidate previously inaccessible mechano-regulated gene expression, chromosome organization and transcription activities in the contexts of cell physiology and pathobiology, including cancer, immunodeficiency and diabetes.

Other UF Health Cancer Center members who collaborated on the research were Shu Wang, Ph.D., assistant professor in the department of biostatistics, and Juan Guan, Ph.D., assistant professor in the department of physics.

Shu Wang, Ph.D.
Juan Guan, Ph.D.
Xin Tang, Ph.D.

The project was funded by the UF Gatorade Award Start-up Package (to Tang), the UF Health Cancer Center Pilot Award (to Tang and Dietmar Siemann, Ph.D., professor and associate director for education and training at the Cancer Center), the UF Opportunity Seed Fund (to Tang), and the UF Health Cancer Center University Scholars Program (to Heyang Wang). The authors also thanked the following Cancer Center leaders for their invaluable support: Jonathan Licht, M.D., director of the Cancer Center; Rolf Renne, Ph.D., professor and associate director for basic sciences at the Cancer Center; Christopher Vulpe, M.D., Ph.D., the team’s gene editing collaborator and professor and director of the CRISPR Functional Screening Shared Resource; and Ji-Hyun Lee, DrPH, professor and director of the division of quantitative sciences.

Hayley Sussman
Miao Huang
Miao Huang
Hitomi Yamaguchi, Ph.D.


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