Inside, blood vessels are lined with a single layer of cells. On their surface, these cells bear specific adhesive proteins by means of which they stick close to each other. Normally, this ensures a perfect sealing of the blood vessels.
The most important adhesive protein is the so-called VE-cadherin. It can be destabilized due to different pathological conditions, e.g. due to a sepsis when bacteria have penetrated into the bloodstream and spread within the whole body. This infection causes inflammatory processes which involve leaks in the blood vessel lining. Blood plasma leaks which might result in life-threatening organ swellings as well as tissue bleeding.
To date, there is no means to seal hyperpermeable blood vessels. However, this would be very helpful e.g. for treating patients with pulmonary edema or allergy-induced organ swelling.
Small peptides ensure adhesion
Here, researchers from the "Institut für Anatomie und Zellbiologie" (Institute of Anatomy and Cell Biology) of the University of Würzburg succeeded in taking a first step forward: They have developed small peptide molecules which increase adhesion between vital VE-cadherin adhesive proteins. Thus, the vascular lining is stabilized against inflammatory stimuli.
How do the peptide molecules work? They work just like an adhesive: They bridge the adhesive proteins with each other, because they are designed following the example of the structure by means of which the VE-cadherins stick close to each other. They have a crosslinking effect which they deploy as tandem peptides arranged one after the other - similar to a medical strip with two adhesive ends.
Still far away from application in humans
"These results offer new approaches for the treatment of vascular hyperpermeability", says Prof. Detlev Drenckhahn. However, it is still a long way to go until an application in humans is possible, because the current structure of the molecules is not suitable for such an application.
According to Prof. Drenckhahn it is always difficult to apply peptides to humans, because an unexpected immune response is possible. The next step for the researchers from Würzburg now is to find other molecules resembling the peptides in structure and effect.
Publication in the Journal of Cell Science
The leading researchers from Würzburg Wolfgang-Moritz Heupel, Jens Waschke and Detlev Drenckhahn describe their new approach in the current issue of the Journal of Cell Science. They have worked together with the structural biologist Thomas Müller from the Biocenter who has developed the peptide molecules on the computer. The peptide molecules have been tested in different systems together with the chemist Athina Hübner, the medical scientist Nicolas Schlegel and other employees of the "Institut für Anatomie und Zellbiologie" (Institute of Anatomy and Cell Biology).
The efficiency of the novel molecules could be shown for isolated VE-cadherin adhesive proteins as well as in vivo by means of atomic force microscopy (AFM): If the protective "adhesive" is injected into the blood vessels of mice, their vascular lining does not break down when being exposed to an experimentally generated inflammatory stimulus.
"Endothelial barrier stabilization by a cyclic tandem peptide targeting VE-cadherin transinteraction in vitro and in vivo", Wolfgang-Moritz Heupel, Athina Efthymiadis, Nicolas Schlegel, Thomas Müller, Yvonne Baumer, Werner Baumgartner, Detlev Drenckhahn, Jens Waschke; J Cell Sci. 2009 May 15;122(Pt 10):1616-1625, doi: 10.1242/jcs.040212
Prof. Dr. Detlev Drenckhahn, "Institut für Anatomie und Zellbiologie", University of Würzburg, phone: +49 (0)931 31-2702, firstname.lastname@example.org
Robert Emmerich | idw
Further reports about: > Anatomie > Anatomy > Small peptides > VE-Cadherin > Vessels > Zellbiologie > atomic force microscopy > blood flow > blood plasma > blood vessel > blood vessels of mice > bloodstream > cell death > inflammatory process > inflammatory processes > inflammatory stimulus > peptide molecules > sealing hyperpermeable blood vessels > synthetic biology
Novel mechanisms of action discovered for the skin cancer medication Imiquimod
21.10.2016 | Technische Universität München
Second research flight into zero gravity
21.10.2016 | Universität Zürich
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...
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...
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...
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...
'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...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
21.10.2016 | Health and Medicine
21.10.2016 | Information Technology
21.10.2016 | Materials Sciences