Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Mechanical tension helps shape lung development

18.02.2005


Findings might help improve lung growth in premature infants



Organ development in the embryo requires precise coordination and timing of cell growth in three-dimensional space to produce the correct anatomic form and shape. Researchers at Children’s Hospital Boston, led by Dr. Donald Ingber, a senior researcher in the Vascular Biology Program, have demonstrated that the process of budding and branching in the developing lung is driven by mechanical forces generated within individual cells. They have also identified a possible biochemical target for intervention. These insights could lead to new ways to prevent, minimize or even correct diseases and anomalies of the lungs, which are common in premature newborns.

Previously, Ingber and colleagues have shown that epithelial tissues – the thin cell layers that line organs and other body structures, including the lung’s airways -- take their characteristic three-dimensional forms through differences in cell growth in different spatial locations. This cell growth is influenced by changes in the extracellular matrix, the flexible, egg-carton-like structure that surrounds and supports cells. Cells are physically connected to the matrix via their cytoskeleton, an internal scaffolding of crisscrossing fibers and tubes that generates tensional forces like those in muscle. Through these tensed connections, cells can "feel" mechanical forces that push and pull on the tissue they are in. If they feel a stretch, cells will begin to proliferate; if they feel compressed, they stop growing and may begin to die off. The parts of the tissue with greater cell growth expand more rapidly than the surrounding areas, causing buds and branches to form.


In this new paper, published in the February 2005 issue of Developmental Dynamics, Ingber and colleagues manipulated the mechanical force felt by developing mouse lungs by modulating the activity of a cellular signaling enzyme called Rho. Rho facilitates a chemical reaction that causes contraction of fibers in the cytoskeleton, increasing tension in the cell and in its connections to the matrix. Ingber’s team put lungs from embryonic mice in culture and exposed them to various chemical agents that stimulate or inhibit Rho’s activity. In normal mice, photographs taken every 12 hours as the lungs grew showed each bud enlarging until a cleft formed in its tip, pinching it into two or three new buds.

When lungs were treated with inhibitors of the Rho pathway, lung bud formation was reduced by more than half when examined 48 hours later. When treated with agents that activate Rho and promote cytoskeletal contraction, budding increased. The agents had similar effects on the growth and development of nearby capillary blood vessels, which must grow in tandem with lung tissue to form a functional organ.

"We’ve showed that we can slow down lung development and capillary growth by decreasing the level of tension in the cytoskeleton, or speed up development by increasing the tension," says Ingber, the Judah Folkman Professor of Vascular Biology at Harvard Medical School. "This work could lead to novel therapeutic approaches to accelerate lung development in premature infants who often are debilitated by incomplete lung formation."

Dr. Stella Kourembanas, chief of Newborn Medicine at Children’s, says that Ingber’s findings could lead to new approaches to treating bronchopulmonary dysplasia, a serious lung injury that affects 30 to 40 percent of all premature babies, and lung hypoplasia, in which the lungs are compressed and cannot develop fully, often due to congenital diaphragmatic hernias, which occur in 1 of 2,500 births. Kourembanas is directing an NIH-funded project on the pathology of lung development, of which Ingber is a part. "Don’s work gives us an understanding of how normal lung growth occurs, and gives us tremendous insights into potential intervention pathways," she says.

Ingber is a pioneer in the new, growing field of mechanobiology--the study of how physical forces affect the function and behavior of living cells and tissues and, ultimately, disease. At the turn of the last century, scientists commonly described biological phenomena in terms of mechanics. "The early developmental biologists watched embryos developing, and saw it as a mechanical process," Ingber says.

This appreciation of mechanics and form fell away as the 20th century progressed. With the advent of molecular biology in the 1970s and 1980s, scientists became focused on finding and mapping individual chemicals and genes as a way of understanding physiology and disease. In this new paper, Ingber and colleagues clearly show that molecular signaling and mechanical forces work hand in hand.

Susan Craig | EurekAlert!
Further information:
http://www.childrens.harvard.edu

More articles from Health and Medicine:

nachricht How cancer metastasis happens: Researchers reveal a key mechanism
19.01.2018 | Weill Cornell Medicine

nachricht Researchers identify new way to unmask melanoma cells to the immune system
17.01.2018 | Duke University Medical Center

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: Artificial agent designs quantum experiments

On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.

We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...

Im Focus: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

Im Focus: Room-temperature multiferroic thin films and their properties

Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.

Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

Let the good tubes roll

19.01.2018 | Materials Sciences

How cancer metastasis happens: Researchers reveal a key mechanism

19.01.2018 | Health and Medicine

Meteoritic stardust unlocks timing of supernova dust formation

19.01.2018 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>