Table of Contents
- Collagen Fibers
- Collagen Function
- Collagen Anatomy
- Types of Collagen Fibers
- Aging and Collagen Related Diseases
- Lesson Summary
Leo is a service dog trained to detect a health crisis in a person with a collagen disorder. He is about to meet the girl he will assist, and we will see who this is in a minute. First, we will explore collagen's function in our body so we can understand the situation.
Pull at your ear lobes, puff out your cheeks, or hang onto the bars of a climbing frame, and you are feeling what collagen fibers do. Collagen is the most common protein in the human body and other mammals, and forms something called connective tissue. Collagen fibers are made of bundles of protein strands that lie on a bed of extra-cellular material outside the cells called a matrix, like spaghetti strands in a lot of thick sauce. Collagen is the most important structural fiber that holds us together. Some collagen fibers are strong and connect muscles to bones as tendons and bind joints as ligaments, while others are stretchy and wrap around things like muscles and the lens of our eye. The soft part of our ear is made of cartilage which contains collagen fibers, our long bones are made of minerals that grow from growth plates which are made of collagen tissue, and skin is held together by a stretchy lower layer called the dermis, which is criss-crossed by collagen fibers that start to sag with age.
The function of collagen fibers is to provide mechanical strength to keep the body together, including when we move. Although bones provide protection and leverage, collagen provides structural support between the bones, holds the organs in place without friction, and connects every single part of the body so it doesn't fall apart.
Collagen fibers are like super-coiled ropes of triple-ply wool. At the tiniest level, three protein strands are wound around each other into what is called a triple helix. This winding occurs inside the cell's Golgi body after the protein is made.
When this short triple helix leaves the cell, it is made into longer fibers. The triple helices are stacked, overlapped, and connected together into bundles called microfibrils (micro means small). You can see the bands of overlapped stacks in an electron micrograph.
The microfibrils are made even stronger by lining up and cross-linking the bundles into a long, parallel fiber called a macrofibril (macro means large). The macrofibril is what we call the collagen fiber. We can see the macrofibrils clearly under an optical microscope when we look at the beautiful parallel strands and matrix of a tendon.
There are four main types of collagen fibers, and other types as well. You hang onto climbing bars using Type I collagen fibers in tendons and ligaments, the strongest and most fibrous type. When you pull at your ear lobe you can feel the looseness of Type II collagen fibers and matrix. Type III wraps around the muscles you use on the climbing bars so they slide over each other freely. When you puff out your cheeks, you can feel the elastic network of Type IV collagen holding your cheeks together.
Type I is the most common type of collagen fiber. The fiber bundles of Type I are organized into dense parallel threads that produce biomaterial that is stronger than steel. Tendons connecting muscle to bones (shown in the image above), ligaments binding bones to bones at joints, the ligament that keeps each tooth from falling out, the fibrous cartilage shock-absorbing disks between our vertebra (shown below/at side), and the collagen in bone are all Type I.
Type II collagen is much looser packed and found in two sub-types of cartilage. Hyaline cartilage has a tough matrix found in the rings around our windpipe, the smooth surfaces on our knee joints, and the shape of our middle nose. The second sub-type is elastic cartilage that is found in our ear lobes and lower end of our nose.
Type III collagen is often associated with Type I collagen, and is a very different stretchy collagen fiber called a reticular fiber. Reticule means a net in Latin. So reticular fibers have short branches going up, down, and sideways, like a net. Type III stretchy fibers are wrapped around the outside of muscle fibers and organs in an elastic sleeve to reduce friction and keep them separated from other parts. These fibers also hold our artery walls together flexibly, absorbing the pulse of pressure created by our heart beat.
Type IV is a non-fibrous structure made of short triple helix sections joined into a net, unlike the coiling of micro or macrofibrils in Types I-III. The structure is similar to a strong elastic version of tennis court netting or a fishing net. You can find Type IV underneath the skin in what is called the dermis, which is the layer below the waterproof keratin layer we see as skin. Type IV is made by epithelia, which are cells that form the body's covering and lining layers. These layers include the lining of lungs, the lining of our cheeks, and even the filtration system of the kidneys.
Sailors in ancient times noticed they had bad gums and their teeth fell out. This was because Vitamin C from fresh fruit is necessary for the body to make collagen. Due to Vitamin C deficiency, the lining of their mouth and the ligaments of their teeth degraded as the collagen aged and was not replaced. Although we are unlikely to have Vitamin C deficiency today, collagen breaks down over time in noticable ways.
Over time, beautifully arranged linear collagen fibers start to break down. The body may repair the fibers but produces a more muddled arrangement that has less elasticity and strength. So the the skin of an older person tends to sag and wrinkle compared with the elasticity of a baby. Smoking has been found to reduce the production and repair of Type I and III collagen under the skin by about one fifth. So smokers tend to have wrinklier, less elastic skin as they get older. The sun also speeds up the breakdown of collagen under the skin, which gets replaced by non-collagen fibers, increasing wrinkles and skin damage. New studies have found that dietary supplements of soluble collagen can assist the skin repair process as people age.
Sometimes the natural repair process is after an injury, and changes the smooth fiber, let's say a tendon, into a rough fiber filled with bits of bone-like calcium, a decay called tendinosis. This may cause friction and pain resulting in tendonitis, the inflammation of a tendon.
Karla is feeling unwell, her heart is racing and she aches badly all over. Her doctors are running against the clock to find out what is wrong, though some people think she is faking it. Finally, they figure it out. Karla has Ehlers-Danlos Syndrome, a disorder of the collagen holding her blood vessels together, making her heart work extra hard and causing all sorts of problems. Although the doctors cannot fix her disorder, they can help her heart manage the situation better with medications.
Ehlers-Danlos Syndrome (EDS) and Marfan's Syndrome are inherited disorders that affect connective tissues containing collagen. EDS is a group of several different collagen disorders that affect 1 in 50,000 people. EDS generally affects the skin and joints, making the collagen very weak, resulting in hyperflexible joints and unusual skin stretchiness (hyper means above or a lot). Karla's type of EDS affects the collagen around her blood vessels, making her arteries and veins super-saggy. This is difficult for the heart to manage in terms of keeping blood flowing well to the upper parts of her body.
To step back and see how these disorders can happen, let's take a look at genes and collagen in more detail. The specific types of protein that collagen's triple helix is made of is coded for by our genes. Unfortunately, some mutations change the sequence of building blocks that make these collagen protein fibers, building blocks called amino acids. When changes in sequence occur, the collagen structures don't form the triple helices propertly, connect the bundles well, or twist the ropes quite correctly. The resulting symptoms depend on the specific details of the syndrome.
Marfan's syndrome is a disorder of the matrix that contains the collagen fibers. People with Marfan's have longer-than-average bones in their arms and legs compared with their torso. The main artery from the heart, the aorta, is very weak and expands much larger than normal. It was rumored that Olympic medallist Michael Phelps had Marfan's syndrome, accounting for his extra reach and flexibility, but this turned out to be not the case.
Scleroderma is another collagen disease (this time not an inherited one) where too many collagen fibers are made, especially in the skin which gets very thick. This is a disease where the body attacks itself, called an autoimmune disease. The body reacts by building up collagen in the skin, blood vessels, and lungs, causing the connective tissues in these organs to harden, tighten, and stop functioning properly. Scleroderma can happen at any time of life, is very difficult to treat, and can cause someone to die. Fortunately scleroderma is rare.
Finally, Leo the service dog has been united with his new owner, Karla! In addition to medications, Leo will help Karla know when she is about to have a heart crisis brought on by her loose collagen. Leo detects the scent change when the crisis is about to occur, when he puts his paw on Karla to alert her, so Karla can lie down and help her heart work better.
Collagen is the most abundant protein in the body. Collagen fibers and the extracellular matrix in which they reside hold the body together in connective tissue. The collagen fibers are made of coiled, stacked ropes of protein. The structure is a triple helix, of protein strands bundled into microfibrils that are packed and connected together in strong, long macrofibrils. The macrofibril bundles are the collagen fibers. There are several types of collagen fibers, the commonest being:
Problems with collagen production and renewal can be caused by aging, smoking, genetic differences and autoimmune diseases:
All parts of the body rely on collagen to function well, and collagen fibers are particularly important to the function of our heart, kidneys, muscles, bones, and skin.
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Collagen fibers provide the strength, structural support, and connecting threads needed by the body to stay together. Different collagen fiber types have different functions, and these include linear strength of tendons, flexible strength of ear lobes, stretchy sleeves around blood vessels, and filtration nets for kidneys and under the skin.
Type I collagen fiber is the most common type, and is found in skin, tendons, and ligaments.
Type II collagen fiber is more elastic and softer, found in nose and ears.
Type III collagen is found with Type I collagen, and is more elastic. This is found around blood vessels, muscles, and organs holding them together.
Type IV collagen is a net that helps the body filter, such as in the kidneys, and keep layers together such as under the skin
Collagen fibers are made of triple helices of protein fibers. These are made strong by building up the helices into bundles called microfibrils, and then grouping these bundles into macrofibrils, which are the strong collagen fibers that we can see under the optical microscope.
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