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Capturing the Extracellular Matrix in 3D Color

Posted on by Dr. Francis Collins

Credit: Sarah Lipp, Purdue University, and Sarah Calve, University of Colorado, Boulder

For experienced and aspiring shutterbugs alike, sometimes the best photo in the bunch turns out to be a practice shot. That’s also occasionally true in the lab when imaging cells and tissues, and it’s the story behind this spectacular image showing the interface of skin and muscle during mammalian development.

Here you see an area of the mouse forelimb located near a bone called the humerus. This particular sample was labeled for laminin, a protein found in the extracellular matrix (ECM) that undergirds cells and tissues to give them mechanical and biochemical support. Computer algorithms were used to convert the original 2D confocal scan into a 3D image, and colorization was added to bring the different layers of tissue into sharper relief.

Skin tissue (bright red and yellow) is located near the top of the image; blood vessels (paler red, orange, and yellow) are in the middle and branching downward; and muscle (green, blue, and purple) makes up the bottom layer.

The image was created by Sarah Lipp, a graduate student in the NIH-supported tissue engineering lab of Sarah Calve. The team focuses on tissue interfaces to better understand the ECM and help devise strategies to engineer musculoskeletal tissues, such as tendon and cartilage.

In February 2020, Lipp was playing around with some new software tools for tissue imaging. Before zeroing in on her main target—the mouse’s myotendinous junction, where muscle transfers its force to tendon, Lipp snapped this practice shot of skin meeting muscle. After processing the practice shot with a color-projecting macro in an image processing tool called Fiji, she immediately liked what she saw.

So, Lipp tweaked the color a bit more and entered the image in the 2020 BioArt Scientific Image & Video Competition, sponsored by the Federation of American Societies for Experimental Biology, Bethesda, MD. Last December, the grad student received the good news that her practice shot had snagged one of the prestigious contest’s top awards.

But she’s not stopping there. Lipp is continuing to pursue her research interests at the University of Colorado, Boulder, where the Calve lab recently moved from Purdue University, West Lafayette, IN. Here’s wishing her a career filled with more great images—and great science!


Muscle and Bone Diseases (National Institute of Arthritis and Musculoskeletal and Skin Diseases/NIH)

Musculoskeletal Extracellular Matrix Laboratory (University of Colorado, Boulder)

BioArt Scientific Image & Video Competition (Federation of American Societies for Experimental Biology, Bethesda, MD)

NIH Support: National Institute of Arthritis and Musculoskeletal and Skin Diseases


  • Zuccheri Gianni says:

    Thinking about a patient.
    Cause of a sarcopenia: abuse of antibiotics, especially quinolones?

    The damage caused to the tendons (especially in the elderly) and to the growing cartilages by some drugs, in particular the antibiotics (especially the quinolones ), is known.

    Abuse of Antibiotics: to this factor could we connect the marked sarcopenia that is accentuated with the passing of the years, in a man not very old (about 65 years)? Starting from about 25 years ago, he had taken frequent courses of quinolones for various causes (bronchitis, prostatitis, infected skin lesions): today these drugs would have been prescribed only for a couple of these episodes; in fact, over time, previously underestimated adverse effects were evident, as one of the many articles suggests:
    Review Antimicrob Agents Chemother . 2012 Aug;56(8):4046-51.
    Adverse effects of antimicrobials via predictable or idiosyncratic inhibition of host mitochondrial components
    Alison E Barnhill 1, Matt T Brewer, Steve A Carlson

    “..their side effects appear to be based on direct inhibition of mitochondrial ribosomes. Chloramphenicol and fluoroquinolones target bacterial ribosomes and gyrases/topoisomerases, respectively, both of which are present in mitochondria. However, the side effects of chloramphenicol and the fluoroquinolones appear to be based on idiosyncratic damage to host mitochondria. Nonetheless, it appears that mitochondrion-associated side effects are a potential aspect of antibiotics whose targets are shared by prokaryotes and mitochondria-an important consideration for future drug design…”

    Congratulations to the authors of this extraordinary 3D image:

    we hope that these researchers with such advanced techniques will help us to evaluate ways of recovering the residual muscle structures: strong rehabilitative physical exercise, intake of vitamins and Coenzyme Q10, future physiotherapy devices.

  • Zuccheri Gianni says:

    Once again I congratulate Sarah Calve and her MEML laboratory team for their interesting searches.

    Not being a researcher, I am hooked to these extraordinary studies with reflections on the conditions to which a preventive solution can be given.

    Muscles, Tendons, Joints … and an unwelcome guest: Periarticular Calcifications.

    These accumulations of calcium in the soft tissues, sometimes asymptomatic, often become a source of pain: I noticed it many years ago, in a scapulo-humeralis periarthritis, probably triggered by excessive exposure to air conditioning.

    Physiotherapy was effective, especially with the use of repeated ultrasound sessions. Shockwaves are also used for this condition.
    The study of the extracellular matrix before and after the destruction of these pathological calcium accumulations probably has a great implication for to understand the etiopathogenesis and the effectiveness of the therapy.

    Thanks to Dr. Collins for his blog and Merry Christmas to everyone!

  • AWB says:

    very nice post

  • Zuccheri Gianni says:

    Regenerative medicine:
    for trauma and inflammation with the application of cold or heat, already in use since ancient times, while nanotechnologies are now being studied for this purpose and for the treatments of neurodegenerative disorders. Biomaterials mimic the environment of the extracellular matrix and allow the growth of different types of cells.

    Vitamin D.
    Vitamin D deficient even in young people during the city winter.
    A 30-year-old girl sent me the blood tests I had prescribed for her fatigue, especially in computer work. Fortunately, everything was normal, including the search for parasites and intestinal diseases: only the vitamin D was unsatisfactory.It is not a rare case, working or studying indoors, prevents the little exposure to the rays of the winter sun (.. if there is)
    The lack of this extraordinary vitamin-hormone, massively affects the health of bones, muscles, tendons and joints: but also our teeth, our psyche and immunity. Rickets arises in the child, while the adult undergoes osteoporosis.

    Osteoporosis … which instead derives from other causes for astronauts, in particular from the absence of gravity. It seemed to me that this is more pronounced in the limbs, in the long bones, rather than in the bones of the vertebrae The effects of microgravity on the musculoskeletal system: with the study of the extracellular matrix and the dynamics of the condition of the mitochondria, from space they will bring results also for common diseases. How many of us have had a muscle tear due to bad stretching!
    In light of all, we could highlight a nutritional and an environmental score, ultimately our lifestyle.

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