Developmental Biology - Autism|
Connection Between Lungs, Oxygen Flow and Disease
New study shows how bacteria alters diseased lung tissue...
A multidisciplinary team of researchers at the University of Illinois at Urbana-Champaign has developed tiny sensors that measure oxygen transport in bovine lung tissue. The study - which establishes a new frame for observing the connection between lung membranes, oxygen flow and disease — is published in the journal Nature Communications.
"The membranes that encase lungs and add the elasticity needed for inhaling and exhaling ... also play a critical role in supplying oxygen to the bloodstream."
Cecilia Leal PhD, Associate Professor and Racheff Faculty Scholar; Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA, and study leader.
For lung tissue to perform effectively, it must be able to transfer oxygen and other gases through its membranes. One way this happens is through a substance called surfactant - which reduces liquid surface tension and allows oxygen molecules to flow through lung membranes.
The tiny new sensors developed by the scientists are made up of thin silicon and graphene films which contain tiny transistors to measure the amount of oxygen exchanged between tissue membrane surfaces.
"A thin film of lung membranes is spread out over many tiny sensors at the device surface, giving us a better picture of what is going on over a relatively large area rather than just a spot," explains professor Leal.
However, a different surfactant called cardiolipin is extremely abundant in lungs infected with bacterial pneumonia.
Cardiolipin (CL) is an important part of the inner mitochondrial membrane and makes up about 20% of mitochondrial lipids. Lipid-anchored proteins are located on the surface of cell membranes, also in the membranes of most bacteria, but are also in plant cells. The name "cardiolipin" comes from the fact that they were first isolated from beef hearts in the early 1940s. Cardiolipin is almost exclusively in the inner mitochondrial membrane, where it is essential for optimal functioning of numerous enzymes involved in energy metabolism.
Researchers used their sensors to compare oxygen transfered between healthy as well as diseased lung membranes. Tissue samples included a bovine lipid-protein commonly used to treat premature infants suffering respiratory distress — while another portion of the samples were combined with cardiolipin.
"We found that more oxygen passes through the diseased tissue by cardiolipin. Which may explain previous observations of an off-balance of oxygen in the blood of pneumonia patients. Even though an increase in oxygen flow could be perceived as positive, it's important to keep a natural [rate of] exchange in the lung - transferring oxygen more rapidly into the bloodstream disrupts healthy equilibrium."
Cecilia Leal PhD
Comparing the structure of healthy and diseased tissue using microscopic and X-ray imaging, researchers found tissue combined with cardiolipin showed damage spots, which they believe are responsible for increased oxygen transfer and subsequent off-balance oxygen levels in pneumonia patients.
The next stage of their research will be studying lung membranes extracted from healthy and diseased mammalian lungs.
"Our results raise important insights on lung membrane function, indicating that changes in structure and composition directly relate to oxygen permeation. This work can potentially enable clinical research examining the role of unbalanced oxygen diffusion through lung membranes in a pathological context."
Cecilia Leal PhD
Lipid-protein complexes are the basis of pulmonary surfactants covering the respiratory surface and mediating gas exchange in lungs. Cardiolipin is a mitochondrial lipid overexpressed in mammalian lungs infected by bacterial pneumonia. In addition, increased oxygen supply (hyperoxia) is a pathological factor also critical in bacterial pneumonia. In this paper we fabricate a micrometer-size graphene-based sensor to measure oxygen permeation through pulmonary membranes. Combining oxygen sensing, X-ray scattering, and Atomic Force Microscopy, we show that mammalian pulmonary membranes suffer a structural transformation induced by cardiolipin. We observe that cardiolipin promotes the formation of periodic protein–free inter–membrane contacts with rhombohedral symmetry. Membrane contacts, or stalks, promote a significant increase in oxygen gas permeation which may bear significance for alveoli gas exchange imbalance in pneumonia.
Mijung Kim, Marilyn Porras-Gomez & Cecilia Leal
Leal also is affiliated with the Beckman Institute for Advanced Science and Technology, the Carle Illinois College of Medicine and the Materials Research Laboratory at Illinois. Kim is a PhD student in electrical and computer engineering and Porras-Gomez is a PhD student in materials science and engineering.
This work is funded by the Office of Naval Research (ONR) grant numbers N000141612886 and N000141812087 (DURIP-Defense University Research Instrumentation Program) and in part by the National Institutes of Health, grant number: 1DP2EB024377 (non-lamellar lipid structures). This research was carried out in part at the Materials Research Laboratory, University of Illinois. This work used resources of the Advanced Photon Source-beamline 12-ID-B, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under contract no. DE-AC02-06CH11357. The authors would like to thank BLES Biochemicals Inc. for kindly providing us with the BLES used in all of our experiments involving lung surfactant extracts.
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Surfactant is a mixture of lipids and proteins. It is secreted into the alveolar to line the sac and lower the surface tension of alveoli in the lung. Bioninja