Collagen-seeking synthetic protein could lead doctors to tumor locations
Pictured are mice injected with a fluorescently tagged peptide that binds to degraded collagen (seen as red) and a commercially available imaging agent that binds to the calcium in bones (seen as green). The mouse on the left was injected with both compounds, and the one in the right was injected only with the collagen mimetic peptide. (Areas where both compounds are present appear as yellow.) The purpose of these tests was to show that the peptides can target bone and cartilage of living animals by binding to degraded collagen. The peptide could someday deliver imaging agents and medications to combat various human disorders such as cancers, arthritis and fibrosis, which are associated with excess collagen degradation. Credit: Catherine Foss and Yang Li/JHU
Johns Hopkins researchers have created a synthetic protein that, when activated by ultraviolet light, can guide doctors to places within the body where cancer, arthritis and other serious medical disorders can be detected.
The technique could lead to a new type of diagnostic imaging technology and may someday serve as a way to move medications to parts of the body where signs of disease have been found. In a study published in the Aug. 27-31 Online Early Edition of Proceedings of the National Academy of Sciences, the researchers reported success in using the synthetic protein in mouse models to locate prostate and pancreatic cancers, as well as to detect abnormal bone growth activity associated with Marfan syndrome.
The synthetic protein developed by the Johns Hopkins team does not zero in directly on the diseased cells. Instead, it binds to nearby collagen that has been degraded by various health disorders. Collagen, the body's most abundant protein, provides structure and creates a sturdy framework upon which cells build nerves, bone and skin. Some buildup and degradation of collagen is normal, but disease cells such as cancer can send out enzymes that break down collagen at an accelerated pace. It is this excessive damage, caused by disease, that the new synthetic protein can detect, the researchers said.
"These disease cells are like burglars who break into a house and do lots of damage but who are not there when the police arrive," said S. Michael Yu, a faculty member in the Whiting School of Engineering's Department of Materials Science and Engineering. "Instead of looking for the burglars, our synthetic protein is reacting to evidence left at the scene of the crime," said Yu, who was principal investigator in the study.
This video is not supported by your browser at this time.A key collaborator was Martin Pomper, a School of Medicine professor of radiology and co-principal investigator of the Johns Hopkins Center of Cancer Nanotechnology Excellence. Pomper and Yu met as fellow affiliates of the Johns Hopkins Institute for NanoBioTechnology. "A major unmet medical need is for a better non-invasive characterization of disrupted collagen, which occurs in a wide variety of disorders," Pomper said. "Michael has found what could be a very elegant and practical solution, which we are converting into a suite of imaging and potential agents for diagnosis and treatment."
The synthetic proteins used in the study are called collagen mimetic peptides or CMPs. These tiny bits of protein are attracted to and physically bind to degraded strands of collagen, particularly those damaged by disease. Fluorescent tags are placed on each CMP so that it will show up when doctors scan tissue with fluorescent imaging equipment. The glowing areas indicate the location of damaged collagen that is likely to be associated with disease.
In developing the technique, the researchers faced a challenge because CMPs tend to bind with one another and form their own structures, similar to DNA, in a way that would cause them to ignore the disease-linked collagen targeted by the researchers.
To remedy this, the study's lead author, Yang Li, synthesized CMPs that possess a chemical "cage" to keep the proteins from binding with one another. Just prior to entering the bloodstream to search for damaged collagen, a powerful ultraviolet light is used to "unlock" the cage and allow the CMPs to initiate their disease-tracking mission. Li is a doctoral student from the Department of Chemistry in the Krieger School of Arts and Sciences at Johns Hopkins. Yu, who holds a joint appointment in that department, is his doctoral adviser.
Yu's team tested Li's fluorescently tagged and caged peptides by injecting them into lab mice that possessed both prostate and pancreatic human cancer cells. Through a series of fluorescent images taken over four days, researchers tracked single strands of the synthetic protein spreading throughout the tumor sites via blood vessels and binding to collagen that had been damaged by cancer.
Similar in vivo tests showed that the CMP can target bones and cartilage that contain large amounts of degraded collagen. Therefore, the new protein could be used for diagnosis and treatment related to bone and cartilage damage.
Although the process is not well understood, the breakdown and rebuilding of collagen is thought to play a role in the excessive bone growth found in patients with Marfan syndrome. Yu's team tested their CMPs on a mouse model for this disease and saw increased CMP binding in the ribs and spines of the Marfan mice, as compared to the control mice.
Journal reference: Proceedings of the National Academy of Sciences
Provided by Johns Hopkins University
- New method to grow synthetic collagen unveiled Sep 08, 2011 | not rated yet | 0
- Synthetic collagen from maize has human properties Jun 24, 2011 | not rated yet | 0
- Scientists create super-strong collagen Jan 12, 2010 | not rated yet | 0
- Nanoscale scaffolds and stem cells show promise in cartilage repair Jul 17, 2012 | not rated yet | 0
- Causes found for stiff skin conditions Mar 19, 2010 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
Ratio of Hydrogen of Oxygen in Dessicated Animal Protein
May 13, 2013 As an experiment, for the past few months I've been consuming at least one portion of Jell-O or unflavored Knox gelatin per day. I'm 64, in very...
Alcohol and acetaminophen
May 13, 2013 Edit: sorry for the typo in the title , can't edit I looked around on google quite a bit and it's very hard to find precise information on the...
Marie Curie's leukemia
May 13, 2013 Does anyone know what might be the cause of Marie Curie's cancer
- More from Physics Forums - Medical Sciences
More news stories
In their quest to learn more about the variability of cells between and within tissues, biomedical scientists have devised tools capable of simultaneously measuring dozens of characteristics of individual ...
Medical research 1 hour ago | 5 / 5 (1) | 0 |
In 2008 researchers from the University of Southern Denmark showed that the drug thioridazine, which has previously been used to treat schizophrenia, is also a powerful weapon against antibiotic-resistant bacteria such as ...
Medical research May 17, 2013 | 3.7 / 5 (3) | 0 |
Scientists investigating the interaction of a group of proteins in the brain responsible for protecting nerve cells from damage have identified a new target that could increase cell survival.
Medical research May 17, 2013 | 5 / 5 (1) | 0
New findings by researchers carrying out experiments at the U.S. Department of Energy Office of Science's Advanced Photon Source (APS) help explain why some drugs that interact with two kinds of human serotonin ...
Medical research May 17, 2013 | 4 / 5 (1) | 0 |
Researchers at the University of Wisconsin have identified a potential new risk factor for obstructive sleep apnea: asthma. Using data from the National Institutes of Health (Heart, Lung, and Blood Institute)-funded Wisconsin ...
41 minutes ago | not rated yet | 0 |
A new study looking at sleep-disordered breathing (SDB) and markers for Alzheimer's disease (AD) risk in cerebrospinal fluid (CSF) and neuroimaging adds to the growing body of research linking the two.
51 minutes ago | not rated yet | 0 |
Gourmands and foodies everywhere have long recognized ginger as a great way to add a little peppery zing to both sweet and savory dishes; now, a study from researchers at Columbia University shows purified components of the ...
41 minutes ago | not rated yet | 0
Scientists at Johns Hopkins have turned their view of osteoarthritis (OA) inside out. Literally. Instead of seeing the painful degenerative disease as a problem primarily of the cartilage that cushions joints, ...
1 hour ago | 5 / 5 (1) | 0 |
The hunt for an HIV vaccine has gobbled up $8 billion in the past decade, and the failure of the most recent efficacy trial has delivered yet another setback to 26 years of efforts.
5 hours ago | not rated yet | 0
The devastating effect of Alzheimer's disease on bilingual people has been thrown into focus in Canada, where the sudden loss of a second language can leave sufferers feeling like strangers in their own country.
3 hours ago | not rated yet | 0