Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers learn how blood vessel cells cope with their pressure-packed job

25.10.2005


UCSD scientists have gained a better understanding of how repetitive stretching of endothelial cells that line arteries can make them healthy and resistant to vascular diseases.


Top: When aortic endothelial cells were stretched in the up-and-down orientation shown here, they grew "stress fibers" (red) in a "healty" alignment perpendicular to the axis of stretch. Bottom: When researchers inhibited a protein called Rho in aortic endothelial cells, stress fibers grew in an "unhealthy" direction parallel to the axis of stretch.


Each of these bovine aorta endothelial cells were stretched along an axis that runs up and down in these photographs. An unstretched cell, top, produced "stress fiber" filaments in random directions, but as the stretching increased from 3 percent of a cell length, middle, to 10 percent of a cell length, stress fibers were increasingly likely to be aligned perpendiculat to the stretching force.



UCSD researchers stretched cells in a workout chamber the size of a credit card to gain a better understanding of how repetitive stretching of endothelial cells that line arteries can make them healthy and resistant to vascular diseases.

Bioengineering researchers at UCSD’s Jacobs School of Engineering will report in the Nov. 1 issue of Proceedings of the National Academy of Sciences (PNAS) that arterial endothelial cells subjected to repeated stretching (10 percent of their length, 60 times per minute) produced intracellular arrays of parallel "stress fibers" in a few hours.


The tests were performed on endothelial cells lining the aorta of a cow, but the endothelial cells of the human aorta are expected to react similarly. The stress fibers were made of actin, a fibrous protein that is part of the machinery that gives muscle its ability to contract. Actin also gives virtually all cells their ability to make an internal "cytoskeleton." The stress fibers of endothelial cells in arteries are aligned parallel to the long axis of blood vessels, and this alignment is perpendicular to the direction of rhythmic stretching caused by a beating heart. Such an orientation of stress fibers is a hallmark of healthy blood vessels, but scientists currently understand few of the factors responsible for generating that configuration.

Rubber bands and most other flexible materials react to stretching by forming stress wrinkles parallel to the direction in which they are being pulled. However, the healthy bovine aorta endothelial cells did not behave that way in tests performed in the laboratory of Shu Chien, a coauthor of the PNAS paper and a professor of bioengineering and medicine and director of the Whitaker Institute of Biomedical Engineering at UCSD. When Chien and his collaborators stretched the cells back and forth along one axis in the miniature workout chambers, the cells formed stress fibers perpendicular to the direction of stretch. "This orientation of actin fibers can be thought of as a feedback control in which the external stresses imposed on the cell are felt internally to a much reduced degree," said Chien.

Post-doctoral fellow Roland Kaunas, now an assistant professor of biomedical engineering at Texas A&M University, with the help of UCSD laboratory assistant Phu Nguyen, found that unstretched cells or cells that were stretched only 1 percent of their length contained actin fibers with no directional orientation. However, as they increased the rhythmic stretching from 3 percent of a cell’s length to 10 percent, stretch fibers became increasingly oriented perpendicular to the stretching direction.

In the most significant finding in the PNAS article, which was made available online Oct. 24, Chien’s group reported that when an intracellular protein called Rho was chemically inhibited, stress fibers grew in the "wrong" direction; they grew parallel rather than perpendicular to the direction of cell stretching. Without Rho, the cells lost their ability to orient stress fibers properly. "Rho is a very important molecule," said Chien. "It works in response to, and in concert with, physical stretching to generate the healthy alignment of stress fibers." Indeed, when Chien’s group used a genetic technique to increase the activity of Rho, those cells grew stress fibers in the healthy direction at a lower threshold of stretching.

"Until now, it has not been shown that there is an equivalence and cooperation between mechanical and biochemical stimuli to regulate the proper orientation of these stress fibers," said Kaunas. "Indeed, we found that the stress fibers oriented in such a way to control their level of stress – not too little and not too much."

Chien and Kaunas collaborated with UCSD research scientist Shunichi Usami, who contributed to the design of the miniature workout chambers. Silicone rubber membranes inside the chambers were coated with a protein that allowed the endothelial cells to adhere to the membranes in a manner similar to how they attach to underlying blood vessel tissue in the body. The researchers isolated endothelial cells from the bovine aorta, grew the cells in culture flasks, and seeded them onto the silicone membranes. After the cells grew into confluent layers, a piston-like "indenter" was programmed to repeatedly push into the underside of the membranes and retract. The 60-cycle-per-minute motion of the indenter simulated the stretching movements of a blood vessel in response to the rising-and-falling blood pressure produced by a beating heart.

The researchers also demonstrated that inhibition of either Rho or a related protein called Rho kinase resulted in loss of the healthy alignment of stress fibers as well as alignment of adhesion sites where those stress fibers would attach to the cell membrane. These new results clearly show that Rho and physical stresses cooperate to produce healthy alignments of stress fibers," said Chien. "We need to understand how cells can sense the mechanical force and achieve this beneficial effect through the activation of Rho, and we also need to identify other proteins that may be involved in this feedback control mechanism."

Rex Graham | EurekAlert!
Further information:
http://www.ucsd.edu

More articles from Life Sciences:

nachricht How gut bacteria can make us ill
18.01.2017 | Helmholtz-Zentrum für Infektionsforschung

nachricht Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

How gut bacteria can make us ill

18.01.2017 | Life Sciences

On track to heal leukaemia

18.01.2017 | Health and Medicine

Water - as the underlying driver of the Earth’s carbon cycle

17.01.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>