Tuesday, February 14, 2012

In lab, Pannexin1 restores tight binding of cells that is lost in cancer

"In healthy tissues, the recently discovered protein Pannexin1 may be playing an important role in upholding the mechanical integrity of the ," said first author and Brown University M.D./Ph.D. student Brian Bao. "When we develop cancer, we lose Pannexin1 and we lose this integrity."

The results appeared in advance online in the on Jan. 20.

To conduct their research, the group at Brown University and the University of British Columbia employed a "3-D Petri dish" technology that allows investigators to watch closely how cells interact with each other, without scientists having to worry about additional interactions with surrounding scaffolding or the culture plate itself. How readily the cells form large multicellular structures therefore reflects their interactions with each other, not their in vitro surroundings.

Bao's advisor, Jeffrey Morgan, associate professor of medical science, developed the 3-D technology. Morgan is the paper's senior author.

Cancer cells converge

Starting with rat "C6" glioma (brain tumor) cells that do not express Pannexin1, the researchers left some unaltered and engineered others to express Pannexin1. After putting the different cells into the 3-D Petri dishes and watching them interact for 24 hours, they saw that the Pannexin1 cells were able to form large multicellular tissues much faster and more tightly than the unaltered .

To confirm that Pannexin1 was indeed causing these changes, Bao and his colleagues treated their samples with the drugs Probenecid and Carbenoxolone, which are well known inhibitors of Pannexin1. They saw that sure enough, the drugs negated Pannexin1's accelerating effect.

Then the team was ready to achieve the the study's main aim, Bao said, namely to determine how Pannexin1 was able to drive these cells to clump together faster and tighter. They found that Pannexin1 sets off a chain reaction involving the energy-carrying molecule ATP and specific receptors for it.

When all experiments were done, Bao, Morgan, and their collaborators had found that as soon as the cells touched each other, Pannexin1 channels were stimulated to open and release ATP. The ATP then bound to cell surface receptors, kicking off intracellular calcium waves that ultimately remodeled the network of a structural protein called actin. This remodeling increases the forces between the , driving them to bind together more tightly.

Figuring out that sequence, and Pannexin1's role in it, is perhaps the study's biggest contribution to cancer research, Bao said.

"Using their single-cell systems, others have been able to carefully study individual pieces of this cascade," he said. "We came from a different perspective. Because the strength of our assay is that we can look at gross multicellular behavior in 3-D, we could ask, 'Does this actually manifest into something tangible on the multicellular level?'"

Having gained this understanding of Pannexin1's role in the mechanics of tumors, Bao is now engaged in research to answer the obvious next questions: Does Pannexin1 affect the tumor's ability to spread and invade? When regain Pannexin1 expression, are they less likely to spread and leave the tumor?

Provided by Brown University (news : web)

Pine transformed by modern alchemists

Pinewood made denser than ebony, textured and hard likes the pure essence of itself? Thanks to a process that reminds one of alchemic essays to turn lead to gold, a team led by Parviz Navi has given simple pinewood similar qualities to wood from expensive and rare tropical species. Starting on the 26th of January, EPFL+ECAL Lab is displaying several objects from daily life made out the new material. Elegant and sleek, objects such as headphones and a door handle show the promising possibilities of the new procedure.

Wood is composed of straw-like tubes filled with air—becoming much denser when compressed. This process has been known for some time now, but until very recently the wood would bounce back into its original form when in contact with humidity. By tweaking the parameters of compression, the EPFL researchers have stabilized the compacted wood without adding any resin or other substance. Suddenly, pinewood loses its working-class roots and inspires for more lofty ambitions—teck, ebony or amaranth.

EPFL+ECAL Lab has called upon Swiss and French designers to create objects out of the new material. Each new project explores a different aspect of the wood. “These first trials are meant to explore the wood’s potential,” explains Nicolas Henchoz, director of EPFL+ECAL Lab.

“We are still in the experimental phase, the procedure will be optimized in the near future in order to move to industrial production,” Henchoz added.

If the bet pays off, it could reduce the burden on tropical forests.

Provided by Ecole Polytechnique Federale de Lausanne

Scientists use silk from the tasar silkworm as a scaffold for heart tissue

Of all the body’s organs, the is probably the one most primed for performance and efficiency. Decade after decade, it continues to pump blood around our bodies. However, this performance optimisation comes at a high price: over the course of evolution, almost all of the body’s own regeneration mechanisms in the heart have become deactivated. As a result, a heart attack is a very serious event for patients; dead cardiac cells are irretrievably lost. The consequence of this is a permanent deterioration in the heart’s pumping power and in the patient’s quality of life.

In their attempt to develop a treatment for the repair of , scientists are pursuing the aim of growing replacement tissue in the laboratory, which could then be used to produce replacement patches for the repair of damaged cardiac muscle. The reconstruction of a three-dimensional structure poses a challenge here. Experiments have already been carried out with many different materials that could provide a substance for the loading of .

“Whether natural or artificial in origin, all of the tested fibres had serious disadvantages,” says Felix Engel, Research Group Leader at the Max Planck Institute for Heart and Lung Research in Bad Nauheim. “They were either too brittle, were attacked by the immune system or did not enable the heart muscle cells to adhere correctly to the fibres.” However, the scientists have now found a possible solution in Kharagpur, India.

At the university there, coin-sized disks are being produced from the cocoon of the tasar (Antheraea mylitta). According to Chinmoy Patra, an Indian scientist who now works in Engel’s laboratory, the fibre produced by the tasar silkworm displays several advantages over the other substances tested. “The surface has protein structures that facilitate the adhesion of heart muscle cells. It’s also coarser than other silk fibres.” This is the reason why the muscle cells grow well on it and can form a three-dimensional tissue structure. “The communication between the cells was intact and they beat synchronously over a period of 20 days, just like real ,” says Engel.

Despite these promising results, clinical application of the fibre is not currently on the agenda. “Unlike in our study, which we carried out using rat cells, the problem of obtaining sufficient human cardiac cells as starting material has not yet been solved,” says Engel. It is thought that the patient’s own stem cells could be used as starting material to avoid triggering an immune reaction. However, exactly how the conversion of the stem cells into cardiac muscle cells works remains a mystery.

More information: Chinmoy Patra, Sarmistha Talukdar, Tatyana Novoyatleva, Siva R. Velagala, Christian Mühlfeld, Banani Kundu, Subhas C. Kundu, Felix B. Engel
Silk protein fibroin from Antheraea mylitta for cardiac tissue engineering, Biomaterials, Advance Online Publication Januar 10, 2012

Provided by Max-Planck-Gesellschaft (news : web)

Researchers develop new drug release mechanism utilizing 3-D superhydrophobic materials

The study was electronically published on January 16, 2012 in the .

Boston University (BU) graduate student Stefan Yohe, under the mentorship of Mark Grinstaff , PhD, BU professor of biomedical engineering and chemistry, and Yolonda Colson, MD, PhD, director of the Dana-Farber Cancer Institute/Brigham and Women's Hospital (BWH) Cancer Center, prepared drug-loaded superhydrophobic meshes from biocompatible polymers using an electrospinning .

By monitoring drug release in and mesh performance in cytotoxicity assays, the team demonstrated that the rate of drug release correlates with the removal of the air pocket within the material, and that the rate of drug release can be maintained over an extended period.

"The ability to control drug release over a 2-3 month period is of significant clinical interest in thoracic surgery with applications in pain management and in the prevention of after surgical resection," said Colson. Colson is also a thoracic surgeon at BWH with an active practice focused on the treatment of .

This approach along with the design requirements for creating 3D superhydrophobic drug-loaded materials, the authors write, should facilitate further exploration and evaluation of these drug delivery materials in a variety of cancer and non-cancer applications.

Provided by Brigham and Women's Hospital