Yale scientists awaken the force in our cells

Friday, October 13, 2023

By Jon Atherton

Researchers at the Yale Nanobiology Institute have developed a new tool to measure how our cells transmit physical force – a trigger for molecular messages and the regulation of major cellular functions. 

Published today in Science Advances, the findings cast light on ‘endocytosis’ – the way our cells absorb and recycle material engulfed by cell membranes.

This process plays a critical role in the way our cells communicate and is therefore a target for therapeutics that tackle the point at which viruses enter our cells.

Scientists have previously realized the importance of force in virtually all cell activities – from how they divide to how they move - but lacked a speedy tool to measure the tension at the molecular scale inside living cells.

Adding a new type of tension sensor to the biologist’s toolkit, the lab of Julien Berro, associate professor of Molecular Biophysics and Biochemistry, and of Cell Biology, has developed a new approach that measures the forces along a key protein linking a cell’s cytoskeleton – the filaments that self-assemble into a powerful engine – to its plasma membrane boundary.

Though imperceptible to humans, their findings suggest that the force received by an endocytic protein is stronger than previously thought – at around 20 piconewtons, or like the pressure exerted by a few hand-held laser pointers.

They also found that the force transmitted to the membrane itself is around half as much, suggesting that other proteins “collect-and-redistribute” force to add robustness.

While previous tension sensors provided valuable information about the ways cells sense forces, major advantages of the new sensors are their smaller size and ease of use.

The new tool measures force along a protein “like opening a mini Velcro strip,” explained Yuan Ren, a postdoctoral associate in the Berro Lab and first author of the study.

“Under higher tension the protein would pull open the mini-Velcro, and that can be detected quite easily,” he explained.  Ren collaborated with Jie Yang in the lab of Yongli Zhang to create and measure the different forces opening along the protein.

By understanding the ways cells transmit force the researchers hope to learn how to manipulate and rewire the proteins to make smarter immune cells that help ward off diseases such as cancer.