Shining Light on Cellular Biomechanics

Associate professor Nada N. Boustany has long been intrigued by the notion of using engineering principles to understand cellular morphology.

“Thinking about the way cells are connected to each other and to the tissue environment that they are in, involves connections inherently related to mechanics,” she says. “As an engineer, you have to think of a cell as controlling inputs and outputs from a mechanical perspective. For instance, a cell controls how much tension it is under and if it is stretched too much, it has to react to counter this and get back to equilibrium.”

For Boustany, whose Bio-optics Laboratory seeks to develop minimally invasive, optically-based quantitative cell analysis methods, a 2017-2018 academic year sabbatical sparked a productive new focus on intracellular biomechanics. Her resulting cutting-edge research is benefiting from both National Science Foundation (NSF) and the National Institutes of Health (NIH) grants.

“I’m very grateful for my sabbatical opportunity,” she says. ”It was absolutely critical in giving me the time to devote to getting into yet into another area or research – and doing it successfully.”

During her sabbatical, Boustany became increasingly interested in learning about the mechanics that control cell morphology  and in understanding how cells respond to their biomechanical environments. “Tissues need a certain structure to function properly, and we are learning that this structure is controlled by biomechanical as well as biochemical signals,” she notes.

In 2018, she received a $465,691 NSF grant that supports an ongoing project that uses a sensor inserted in the protein vinculin to measure tension and force in a cell using fluorescence resonance energy transfer, or FRET.

“When one cell attaches to another or to the extracellular matrix, it’s bound to experience a force at that location. When there’s a FRET tension sensor in a protein like vinculin that sends signals from that location, we can measure this  force,” she explains.

In 2020, Boustany received a $92,910 GOALI – Grant Opportunities for Academic Liaison with Industry – grant that supplements her initial NSF award. In collaboration with Thorlabs Inc., she is using it to develop a fluorescence lifetime imaging microscopy, or FLIM, system to help her measure FRET in her lab. “My sabbatical opened up all these avenues of looking at this topic in my own microscopy platform in my lab, with the assistance of graduate and undergraduate students,” Boustany says.

This year, Boustany and Bonnie Firestein, a School of Arts and Sciences professor of cell biology and neuroscience, received a two-year $431,444 National Institutes of Health NIH-R21 grant for their project that will use FRET-based sensors to image protein kinase A activation to explore mechanisms of dendrite development and branching in neuronal cells and repair after injury.

Boustany is also collaborating with French researchers with the goal of combining a FRET tension probe with optical tweezers that can trap particles in a focused laser beam in order gain additional understanding how force is transmitted as a cellular signal.

In considering the big picture, Boustany notes that diseases can develop when a cell cannot process the mechanical signals it receives. “Cells can migrate or proliferate too much and can’t repair themselves, or die,” she says. “The challenge ultimately will be to develop drugs that can treat disease by addressing and adjusting mechanical signaling.”