“Molecular Velcro” allows tissues to sense and respond to mechanical forces

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University of Illinois professor Deborah Leckband led a study that revealed how Velcro-like cellular proteins called cadherins sense tissue mechanics to regulate cell communication and biological tissue growth.

Photo courtesy of Claire Benjamin

CHAMPAIGN, Illinois – The velcro-like cellular proteins that hold cells and tissues together also perform critical functions when subjected to increased stress. A new Urbana-Champaign study from the University of Illinois observed that these proteins — called cadherins — communicate with growth factors when tightened in a controlled manner to affect tumor growth in human carcinoma cells in vitro.

The study, led by Deborah Leckband, professor of chemical and biomolecular engineering, found that cadherins, which bind to growth factor receptors, can sense and respond to mechanical forces by altering cell communication and cell growth.

The results are published in the Proceedings of the National Academy of Sciences.

When growth factor receptors are attached to cadherin molecules in normal tissue, they can’t communicate with growth factor proteins – the substance they need to promote tissue growth. However, the study shows that changes in cadherin bond strain disrupt cadherin-growth factor interaction to turn on growth signals in tissues.

To demonstrate how stress affects tissue growth, the researchers set up an experiment to observe how human carcinoma cells convert mechanical information into biochemical signals in vitro, Leckband said.

The team used a homemade ‘cell stretcher’ in which the carcinoma cells are grown in a thin layer on the surface of a flexible medium. When the cells are stretched, the researchers observed changes that could increase tissue growth and tumorigenesis.

“This study confirms that cadherins use force to turn on biochemical growth signaling,” said Leckband. “By confirming these force-induced disorders, we may be able to find a way to mutate cadherin molecules to prevent certain types of tissue growth, such as B. metastatic transformation and tumorigenesis.”

The team has observed the cadherin growth factor receptor complex in human epithelial tissue and plans to extend this concept by working with human breast tissue in vitro.

Brendan Sullivan and Vinh Vu, Illinois graduate students; Student Adrian Kapustka; and researchers from Johns Hopkins University contributed to this study.

Leckband is also a professor of chemistry and bioengineering and is affiliated with the Beckman Institute for Advanced Science and Technology, the Carl R. Woese Institute for Genomic Biology, and the Nick Holonyak Micro and Nanotechnology Laboratory.

The National Institutes of Health supported this study.

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