Menu

Cells Follow Stiffness Gradients by Playing Tug-of-War

Cells with the best traction on a substrate pull their neighbors toward firmer ground.

Dec 1, 2016
Ben Andrew Henry

PULLING THROUGH: Groups of human epithelial cells migrate toward firmer ground due to linkages between cells and traction with the substrate. Cells adhere to their neighbors through intercellular junctions, which are connected to myosin motor proteins within each cell. The myosin motors cause the cells to contract and tug on one another, but cells residing atop firmer substrate get a better grip through integrin proteins and are therefore able to pull the group in their direction. © GEORGE RETSECK. ADAPTED FROM SUNYER ET AL., SCIENCE, 353:1157, 2016. REPRINTED WITH PERMISSION FROM AAAS

EDITOR'S CHOICE IN CELL & MOLECULAR BIOLOGY

The paper
R. Sunyer et al., “Collective cell durotaxis emerges from long-range intercellular force transmission,” Science, 353:1157-61, 2016.

The physical features of a cell’s surroundings—the texture of a substrate and the push-pull of intercellular forces—have often taken a back seat to scientific interest in the chemical environment of cells. But biologists are finding time and again that physical signals matter. In 2000, researchers observed that fibroblasts embedded in a gel migrate toward areas where the gel is stiffest—an apparent response to physical rather than chemical signals termed durotaxis. The discovery turned heads. The report attracted almost 2,000 citations over the next decade and a half, and it became a cornerstone of the emerging field of mechanobiology, says Xavier Trepat, who studies durotaxis at the Institute for Bioengineering of Catalonia in Spain.

Exactly how cells “durotax” has been a mystery. Available research implicates durotaxis in a number of important cellular processes, from neuron development to cancerous tumor formation, but “there are only a few papers out there proposing mechanisms,” Trepat says, none of which give a definitive explanation.

Trepat and his colleagues studied the problem using traction force microscopy, which involves embedding fluorescent nanoparticles into a gel substrate and tracking the particles’ displacement. As cells drag themselves around on the gel substrate, they leave a record of the forces they exert, allowing researchers to decode the physics at play.

When Trepat and his team placed mammary epithelial cells on a gel substrate of graded firmness, they saw the cells durotax, but also noticed something strange. Only cells in a group moved toward the stiffer area, whereas solitary cells moved randomly. The team’s effort to explain this quirk led them to a molecular and mathematical theory of durotaxis.

Researchers had already known that epithelial cells move around by linking onto each other with protein junctions and pulling on the substrate with myosin motor proteins, like someone climbing a rope. Using traction measurements, Trepat and colleagues revealed that epithelial cells in a group do not all move in coordination, but that each edge of the group pulls outward at the same time. Cells sitting on stiffer substrate get better traction, so they win this tug-of-war, and the whole group moves toward them. Durotaxis is not a complex signaling process, they realized, but the result of simple physics.

The discovery brings some clarity to a young field still rife with questions. “Cell migration and cell growth have been studied for decades now, but people have not thought about forces,” says Kristian Franze, who studies mechanics in nervous system development and pathology at the University of Cambridge.

“This paper just makes so much sense,” Franze says, but adds with a laugh that in the field of mechanobiology at large, “we barely know anything.”

February 2019

Big Storms Brewing

Can forests weather more major hurricanes?

Marketplace

Sponsored Product Updates

Bio-Rad Showcases New Automation Features of its ZE5 Cell Analyzer at SLAS 2019
Bio-Rad Showcases New Automation Features of its ZE5 Cell Analyzer at SLAS 2019
Bio-Rad Laboratories, Inc. (NYSE: BIO and BIOb) today showcases new automation features of its ZE5 Cell Analyzer during the Society for Laboratory Automation and Screening 2019 International Conference and Exhibition (SLAS) in Washington, D.C., February 2–6. These capabilities enable the ZE5 to be used for high-throughput flow cytometry in biomarker discovery and phenotypic screening.
Andrew Alliance and Sartorius Collaborate to Provide Software-Connected Pipettes for Life Science Research
Andrew Alliance and Sartorius Collaborate to Provide Software-Connected Pipettes for Life Science Research
Researchers to benefit from an innovative software-connected pipetting system, bringing improved reproducibility and traceability of experiments to life-science laboratories.
Corning Life Sciences to Feature 3D Cell Culture Technologies at SLAS 2019
Corning Life Sciences to Feature 3D Cell Culture Technologies at SLAS 2019
Corning Incorporated (NYSE: GLW) will showcase advanced 3D cell culture technologies and workflow solutions for spheroids, organoids, tissue models, and applications including ADME/toxicology at the Society for Laboratory Automation and Screening (SLAS) conference, Feb. 2-6 in Washington, D.C.
Corning Introduces New 1536-well Spheroid Microplate
Corning Introduces New 1536-well Spheroid Microplate
High-throughput spheroid microplate benefits cancer research, drug screening