Flipping a nano-scale molecular switch may regulate the cell-binding function of a protein involved in healing and other fundamental biological activities. Computer simulations show that, like untying a shoelace, tugging on a strand of the protein fibronectin unravels a loop critical to cell recognition but otherwise leaves the protein intact for reactivation.
Reporting in the Feb. 16 issue of the Proceedings of the National Academy of Sciences, researchers at the University of Washington and the University of Illinois at Urbana-Champaign describe this as the first illustration of how the body may use tension-activated switch mechanisms to regulate biological function.
"Understanding how nature has evolved these systems gives us insight into basic cell biology as well as elegant design principles for mechanical switches in biotechnology devices," says senior author Viola Vogel, associate professor of bioengineering and director of the Center for Nanotechnology at the UW. "Since nano-scale tools have only recently been developed for analyzing the mechanics of single molecules, we are entering a new era of understanding how molecular mechanics control biological activity."
Vogel's research, funded by the National Institutes of Health, is particularly interested in fibronectin, a glycoprotein that is a major building block in the cell-surface network known as the extracellular matrix. The extracellular matrix regulates adhesion, communication, gene expression and other interactions between the cell and its environment. Thus, it is of keen interest to scientists studying basic cell biology as well as engineers designing artificial devices to integrate naturally into the body.
Fibronectin is comprised of a chain of repeating modules, only one of
which contains the specific RGD tri-peptide loop responsible for cell adhesion.
This module - labeled FnIII10 - consists of seven connected beta strands folded
Contact: Greg Orwig
University of Washington