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Jing Liu awarded NSF and NIH grants to study mechanics in human cells

2024-05-02

Human cells generate and sustain mechanical forces as part of their normal physiology. These forces, typically in the scale of several to tens of piconewton (10-12 N), could easily control the structures and biological functions of the cell. A newton is a unit used to measure force and a piconewton is one trillionth of a newton. Detecting forces in this scale is really challenging, particularly in a live human cell. Jing Liu, associate professor at the Purdue Department of Physics and Astronomy, has integrated modern molecular biology techniques with imaging methods to detect the piconewton forces generated inside a living cell.

“This precise measurement was enabled by a molecular biosensor based on the Forster resonance energy transfer (FRET)” says Liu. “This tension sensor was purified from the spider silk protein and is about 15 nm long; it acts as an entropic spring to report the bearing forces produced by the cell. Our lab has collaborated with molecular biologists to insert this tension sensor into different motor proteins inside the cell to measure the mechanics in cell focal adhesion that is important for cell migration, and in cell membrane and skeleton that are critical for cell architectures.”

Liu’s lab is collaborating in cutting-edge mechanics-driven biophysics and medical research which has recently gained him two grants to study cell migration and cells in the human eye.

One of the two grants awarded to Liu is a joint National Science Foundation (NSF) and National Institute of Health (NIH) grant titled “DMS/NIGMS 1: Simulating cell migration with a multi-scale 3D model fed by intracellular tension sensing measurements.” This three-year $600,000 collaborative grant with be used by Jared Barber , associate professor of mathematical sciences at  IUPUI, and Liu. The two will combine live-cell force sensing with mathematical models to understand how internal forces of a cell respond to the properties of the surrounding, external environment and drive cell migration. The outcome, in turn, will lead to a better understanding of how to inhibit (such as with cancer) or promote (such as with healing wounds) cell migration to improve patient outcomes.

The second of Liu’s grant awards will come from the NIH R01 grant (1R01EY035412) which is titled, “Transcriptional control of lipid biogenesis in trabecular meshwork and intraocular pressure regulation.” This is a collaborative four-year grant for $1.8M. This grant is funded by the National Eye Institute to support a collaborative team with researchers from IU School of Medicine, Purdue, and UIUC. Padmanabhan Pattabiraman, assistant professor from the Indiana University School of Medicine, is the principal investigator for this grant and will lead the multidisciplinary team to investigate the molecular mechanism of glaucoma.

“For the NIH R01 grant, my team will apply the imaging-based force sensing approach to assess the real-time changes in membrane tension of trabecular meshwork cells upon the protein activation/inhibition," says Liu. "This will help us to understand the mechano-regulation of the trabecular meshwork cells."

“Multidisciplinary approaches that integrate modern molecular biology techniques, advanced force sensing methods, and mathematical modeling now pave the way towards better understanding the role of mechanics in disease initiation, development biology, and physiology,” added Liu. “There is significant overlap between physics and biological sciences, and this collaborative scientific approach would lead to giant leaps in medical advances.”

cellillustration_liu.png
In the illustration above, a cell produces more forces (red -> blue) on focal adhesions to migrate. Illustration provided by Jing Liu.

 

 

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Contributors:   

Jing Liu, associate professor in the Department of Physics and Astronomy at Purdue University  

Written by Cheryl Pierce, Communications Specialist

Last Updated: May 3, 2024 7:59 AM

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