Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

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

03.12.2003


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:
http://www.uiuc.edu/

More articles from Health and Medicine:

nachricht New malaria analysis method reveals disease severity in minutes
14.08.2017 | University of British Columbia

nachricht New type of blood cells work as indicators of autoimmunity
14.08.2017 | Instituto de Medicina Molecular

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: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

New bioimaging technique is fast and economical

21.08.2017 | Medical Engineering

Silk could improve sensitivity, flexibility of wearable body sensors

21.08.2017 | Materials Sciences

On the way to developing a new active ingredient against chronic infections

21.08.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>