Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Unraveling a protein, researchers uncover mechanics of anti-cancer agent


From within the rich fabric of connecting tissue between cells, researchers of four institutions, led by the University of Illinois at Urbana-Champaign, have identified the action of anastellin, a natural agent that is showing promise blocking metastasis of cancer cells and enhancing wound healing.

FN-III-1 during unraveling (bottom). Red (top and below) depicts the strong sheet (anastellin). Green depicts the weak sheet.
Credit: UIUC

That anastellin is derived from the cell adhesion protein fibronectin found in the extracellular matrix surrounding cells was known. Researchers at the Burnham Institute in California in September had documented the molecular structure of anastellin, but its ability to initiate matrix assembly and block the spread of cancer cells remained a mystery.

Using crystallography, atomic force microscopy and advanced computer modeling, researchers sorted the chemical structure and mechanical strength of the known fibronectin proteins that glue together myriads of cells in mammalian body tissues.

In the Dec. 9 issue of the Proceedings of the National Academy of Sciences,
they show that the fibronectin known as FN-III-1 behaves differently mechanically than other type-three modules. The paper was placed online Dec. 1 at the PNAS Web site.

"Type 3-1 stands out," said Klaus Schulten, holder of the Swanlund Chair in Physics at Illinois and director of the theoretical and computational biophysics group at the Beckman Institute for Advanced Science and Technology.

"When stretched mechanically, it extends in two stages, first to about one-third of its total length, then to full length, or about 10 times its initial size," he said. "The first stretch reaches a rather stable intermediate. Other fibronectin type-three modules reach their extended length more quickly."

All fibronectin type-three modules consist of a sandwich structure containing two sheets, but Schulten and his colleagues found that one sheet of 3-1 is much stronger.

"It is mainly this strong sheet that is anastellin, and it stabilizes the stretching intermediate by refusing to unravel," said Viola Vogel, professor of bioengineering and director of the Center for Nanotechnology at the University of Washington at Seattle.

"Research has shown that cells can apply sufficient mechanical force to the surrounding extracellular matrix to unravel fibronectin type-three modules," she said. "The stretching of 3-1 unmasks the buried anastellin. It appears to restrict the motion of cancer cells, in effect creating strong jail bars that hold the cancerous inmates from moving freely."

"To understand how this is done," Schulten said, "one must know that the extracellular matrix is an intelligent fabric. It connects cells, guides their movements and communication, and acts as glue between cells in living tissue, strengthening when needed."

The matrix is made of several types of proteins, not just fibronectin. Each has a distinctive chemical composition and structure. The proteins are like knots in a net, forming a network of fibrils. As the network is stretched, the proteins change their structures and expose chemically active groups. Once exposed, anastellin enhances the ability of the proteins to form networks.

"The cells use anastellin apparently when it arises in half-unraveled FN-III-1 to strengthen the glue effect of the matrix," said Mu Gao, a doctoral student studying with Schulten at Illinois. "Anastellin acts as part of FN-III-1 or by itself as an anti-cancer drug."

Unraveling of fibronectins is determined by the arrangement of the some 100 amino acids within them, said David Craig, a former graduate student in bioengineering at the University of Washington. FN-III-1’s amino acids form hydrogen bonds among themselves and are organized to create the strong-weak-sheet protein structure. Nuclear magnetic resonance unveiled the amino-acid arrangement that makes up the protein structure.

Jim Barlow | EurekAlert!
Further information:

More articles from Health and Medicine:

nachricht Resolving the mystery of preeclampsia
21.10.2016 | Universitätsklinikum Magdeburg

nachricht New potential cancer treatment using microwaves to target deep tumors
12.10.2016 | University of Texas at Arlington

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Resolving the mystery of preeclampsia

21.10.2016 | Health and Medicine

Stanford researchers create new special-purpose computer that may someday save us billions

21.10.2016 | Information Technology

From ancient fossils to future cars

21.10.2016 | Materials Sciences

More VideoLinks >>>