Fibers

Didn't we already discuss fibers? Yes. But as this is a pediatric orthopedic site, we need to zoom out a bit from the atomic to the more grossly cellular. But a brief recap:

Actin filaments are long polymers that wind in twos as a spiral. Actin will be adorned with an array of other substances so as to make the actin form rope-like clusters or grids that make gels. There are several large molecules which can pull along actin and can drag cellular elements to destinations along the actin paths.

One such substance, in the cell, is myosin. Myosin has a long tail and a thick head which is composed of several sub units. The head part can take in ATP which causes it to open its mouth (and lose its grip on what it is biting), bend at the neck, and bite again. The ATP spring drives this. The presence of ATP and Myosin and its chewy toy - actin - would have myosin nibble its way to the end of the actin and just sit there able to go no further.

The energy to traverse the actin by using up ATP lacks control. Thus control must be added to this system. As we see it here, the myosin is a so called Type I, that is loner myosin - single strand type as would be fitting dragging small stuff around inside a cell.

But actin alters its organization and behavior by the company it keeps. Inside the generalized cell it varies by the functional needs from location to location.

But muscle is specialized.

In muscle, the need is that of the colony and not the cell itself. That requirement is external and uniform. Therefore the actin and myosin of muscle are much more specialized and souped up.
We see, above, a piggy back strand (shown in blue) on the actin called tropomyosin. The tropomyosin is fairly straight and stiff. It makes the third strand of the actin/actin/tropomyosin composite rope.

Piggy back on the tropomyosin at intervals is a three part protein whose structure is nearly identical to another cell protein called Calmodulin - a strong attractor of Calcium ion. If there is Ca⁺⁺ floating about, it will be attracted to the rider on the tropomyosin.

How it almost works:

In a test tube, myosin with ATP will zing to a final end walk position with nowhere else to go. All you need is actin, myosin and the ATP => boing, it goes. But muscle cells always have actin and myosin and the ATP is nearly always at capacity concentration (a curiosity to be explained later).

The question is how does muscle NOT work? The probability is contraction. The end state is contraction. Rigor mortis is contraction end state. What makes it not go? Life is controlled improbability.

Well that (blue) strand of tropomyosin does not just coil the actin willy-nilly, it covers most of the myosin grab points. Myosin can't walk along the actin with those grab points covered. When it is time to contract, the cell dumps a gush of Ca⁺⁺ into the cell. That calcium ion gets sucked into the thingy on the tropomyosin (the calmodulin looking thingy), which causes the tropomyosin to roll aside and uncover the actin grab areas. Once those are exposed, myosin does its natural thing and runs along the actin.

Smooth muscle has actin strung across the cell in X patterns. But in skeletal muscle the structure is highly parallel and organized as bundles of repetitive parts.

Myosin II, or just plain "myosin" in the context of this discussion, can be grouped like a bouquet of flowers, as seen in an overly small grouping above (for clarity). But the bundle puts the flowers at both ends.

Bundled myosins are encircled by parallel actin (duel actin + tropomyosin) strands. The actin attaches mechanically at plates called Z-Plates, named after a famous Spanish American folk hero (or not, it could stand for 'Zah end'). The polarity of actin is such that two groups of actin get pulled together toward center (M in the middle) as shown by the arrows. There are other fibers whose job is to suspend this stuff.

OK. We have the basic goods. What makes it go? A signal. A signal says "do it" and calcium ion gets dumped. From where? Around each unit, in a fine mesh-like system of sacs (pink above) called sarcoplasmic reticulum (sarco=muscle, plasm=in the gooey part, reticulum=mesh like - not solid) is a whole bunch of Ca⁺⁺ just ready to go. On the signal, those membrane spigots open and the Ca⁺⁺ floods out into the muscle unit. It contracts.

Skeletal muscle looks like this under a microscope. Each color zone got a designating letter that in retrospect could have been better thought out. A,B,C or runes, who cares. We now know that this stripe pattern is from the overlap of actin and myosin. The actin ends and attaches at the Z part. How big the stripes are just reflect the degree of contraction of the muscle as it is observed.

The books all stop here. Story over. Holdit. That can't be all?? OK. Speculation follows. We know that when whole muscle is stimulated to contract, heat is given off. However, that heat is given off during RELAXATION, it is called heat of relaxation. Whenever heat is given off, generally something important is happening. What? Well for one thing, if those calmodulin-like tropomyosin thingies so attract calcium ion, how do you get it all back?

You work for it. Pure and simple. It requires a pump and lots of energy to pull that calcium back into the sarcoplasmic reticulum storage. In a sense, the real energy of muscle contraction is done during relaxation as is the case with a setting cross bow. Work is done to set it up so that it can spring quickly and powerfully at a moment's notice.

This is very important to us as observers of exercise and big functional activities such as walking. The further the myosin pulls the actin together, the more work (fuel) will be needed to reset it to starting length.

3 Cases:

1: Stimulus => full unit shortening. The muscle moves something through its full range.
           We call this muscle contraction.

2. Stimulus => no shortening at all. The muscle just keeps something where it was.
           We call this muscle contraction.  uh, wasn't that term already taken...

3. Stimulus => muscle actually elongates. The external object pulls enough to elongate an
           activated muscle unit
           We call this muscle contraction. Whoa! That's out and out confusing!!

That's right. The term muscle contraction is essentially USELESS! It has been so muddied by misuse that it no longer means anything.

We will call it muscle activation when a stimulus sets the chemistry in motion. That says nothing about what actually happens to length. The first case of actual shortening is called concentric muscle activity. The second case, where length is unchanged, is called isometric muscle activity. The last case, the really weird one, the most improbable of the bunch, wherein muscle elongates in active state, is called eccentric muscle activity.

The biggie? Well, about 99% or better of muscle activity is eccentric in walking - that is in walkers walking.

Didn't expect that, did you? We will visit that in the next section. About that ATP mystery. Why isn't the ATP consumed? It is - but it is simply replenished pronto by the real energy reserve of muscle called Creatinine Phosphate.
                  OH
                  |
                  C=O
                  |
                H C H
                  |
             H₃ C--N H₂
                  |
             H N--C=N H
               |
              PO₄  (or  H)   <= This phosphate very quickly recharges the ATP which is spent down to ADP as the myosin does its AC/DC head flailing walk down the actin. The creatinine Phosphate is what gets depleted. Why this substance? Because it is a fast in-out energized P transport between the muscle filaments area and the goings on in mitochondria where the high energy gets generated. Those mitochondria are shown in light blue in the image of the actin-myosin functional unit above

       Na⁺     Na⁺  Na⁺        Na⁺ Na⁺     Na⁺        Na⁺
Na⁺            Na⁺   Na⁺      Na⁺               Na⁺         Na⁺ Na⁺
      Na⁺     Na⁺        Na⁺   _signal=> Na⁺   Na⁺       Na⁺     Na⁺       Na⁺  Na⁺
=====: Na⁺ _| :=========<: :>========: :=========: :========: :=======::=cell membrane
  K^{+    |}   K⁺   K⁺        K⁺     K⁺          K⁺    K⁺  K⁺     K⁺   K⁺    K⁺
     K⁺     K⁺    K⁺         K⁺     K⁺         K⁺      K⁺ K⁺    K⁺   K⁺     K⁺
   K⁺                  K⁺    K⁺        K⁺             K⁺      K⁺      K⁺

The signal to dump calcium ion is an electrical charge that sweeps along muscle cell membrane. As the cell membrane sequentially opens pores, potassium (K⁺) and sodium (Na⁺) swap places. The potassium concentrated inside the cell, flushes out. Sodium, in higher concentrations outside, swoops in. The membrane resets by closing those Na/K specific pores and turning on the sodium potassium pumps so as to put things back the way they were.

Most of the creatinine phosphate is ultimately derived , at slow paced activity, from the fat storage mechanism via the cycle described previously. But if pushed to a frenzied pace, the anaerobic muscle can keep ahead as the citrate cycle mechanism falls off dependent on O₂ delivery. Hence higher need for 'carbs' with lactic acid production. Accumulation of lactate also occurs as removal uses the same limited delivery system as O₂ - blood flow..

One interesting outcome of this is that when the overall body mass of muscle is very low, then what is left works very hard as the load isn't being shouldered by other units. That may result in more lactic acid being produced than would be otherwise expected. We have witnessed the control of acid base disorder in certain enzyme deficiencies just by increased muscle mass alone ( and subsequent decreased lactic acid acid muscle output). That's not common, but is illustrative.

Collagen & Elastin

The framework that holds us together

.The cloth of which we are made is akin to what we use to dress ourselves. Basically two types of threads are used. One is tough and makes the cloth that binds the organs and links things together - collagen. The other is stretchy and allows tissues to yield and contour - elastin.

Collagen is made up in many tissues much the same as threads or ropes, with twisted fibers twisted about other twisted fibers.

We start with the amino acid core unit. It has a basic C-C-N form (two carbons and a nitrogen). The end nitrgen with hydrogen on the open bonding areas is the amine (hence amino). The end carbon is has oxygen and hydroxyl terminating its free bonds. That is an acid, -COOH, hence amino 'acid'.

^H   X
HN--C -- C=0
         0H

The ^X part is different for each amino acid. In the simplest case the X is just hydrogen. In more complicated amino acids the X part can be quite involved.
The point is that the N--C -- C portion repeats and becomes the string that links the various pearls:

  ...N--C -- C--N--C -- C-- N--C -- C--N --C -- C--...

and so on.
The ^X part (in the image as a blue smudge) gives the quality to each unit. That x portion may be oily, or something that wets readily (likes water) or has a high electric charge, or is tangled, or extends way out and offers a linkage or causes the chain itself to bend a certain way. Nearly a full alphabet of variations make up the alphabet of amino acids. They get strung together the way letters get strung in a line to make a kind of sense. But note that the string tends to curl up like a slinky. Three amino acids in a row make a near full wind.

The side parts (the X bits) interact and glue this spiraled chain quite solid. Even though it begins as a coil, it behaves as a rod. The rod itself isn't exactly straight. It, too has a gentle coil shape. It is called an alpha chain for some excrutiating reason.

Every third amino acid in collagen has a nothing X side thingy (just a small hydrogen rather than anything fancy. Called glycine) With all that other stuff sticking out, and with this repeating flat glycine area (which attracts a certain way), the result is that three of these collagen proteins coil about themselves into a long twisted thread of three proteins. The multicolor reduced magnification version is shown above on the right and behind the magnified single strands.

That's collagen. Sort of. Well not just any three proteins twisted. They all have that glycine every third thing going on. But there are about a dozen variations in how the X parts are configured which alter the way the threads link into a twist (or maybe don't twist at all) or cross link to form sheets.

Think about it. You can have a racoon tail or a porcupine tail, or cotton candy like structure depending on the bits that stick out (like bristles from a bristle brush). Hey. That's good. A bristle brush has a central twisted stiff long core and bristles of whatever property is need for the intended job. Yeah. I like that. Good.

Collagen gets described by naming the three thread subportions. There are three most common alpha chain types. Alpha-1, alpha-2 and guess the next..

yeah [ alpha-3 ] <=highlight to see the tricky answer.

Well, collagen type I is made of two a-1 chains and one a-2. This is the type in bone and tendon and mixed with others in skin and blood vessels.

Collagen type II is made up of three a-1 threads. This collagen is key to cartilage, vertebral disks, and the gooey part of the eye. Those bristles have certain sugar bits attached which really like water.

So, collagen forms strings which are woven through tissue or into ligaments and tendons. But, too, some versions form sheets. The basement membranes which hold cells in place and which serve as filters are of collagen (types IV and VII).

There are others. Just know that the common thread is - uh - thread.

Compare collagen shown in blue with red side thingies, with elastin shown in yellow.

The curly protein shape of elastin proteins and weird cross links going every which way, allow elastin to spring back after stretching, whereas collagen doesn't give so much.

How are these protein sequences put together? From a recipe! DNA sequences code the sequences for each protein but with handles initially.

  STARTGooberGooberThe_Protein_Part_Is_This_PartGooberGooberEND

This gets made then a snip process which recognizes goobers removes the handles:

STARTGooberGoober

The_Protein_Part_Is_This_Part

GooberGooberEND

In the goober handles which get trimmed is code that tells the cell WHERE THIS THING IS TO GO!!! ! It is a mailing address!!! If the protein part is good but the code for the address has an error, guess what? Yeah. The mail isn't delivered.

Think of how many ways this sequence can get muddled. That's about the number of versions of Ehlers-Danlos syndrome there are. If collagen does not work or get to where it has to go, then elastin is used instead.

Ahhh, but there are different kinds of collagens using different alpha chain trios. Sooo, not all collagen locations are affected, right?

Right. Sometimes vessels are way bad and other times not. Sometimes the skin falls apart and other times not too bad.

But what happens if the handles of the collagen don't get snipped off so that the cell can expell the final product? Well if that defect is happening to type I collagen, we have osteogenesis imperfecta - brittle bones disorder. Remember bone is not calcium. Calcium (as a crystal called hydroxy appetite) merely hardens the cloth we call bone. Bones depleted of calcium by acid can be tied in knots - but they are still bones. However, without the fiber basis, the core collagen framework, it becomes chalk - brittle.

If the collagen can't nestle together because a glycine (having no stickyout thingy) gets substutited by an amino acid with aside bit sticking out, then the coil gets screwed up. How bad the inability to coil the triple protein thread or how deficient the delivery determines how severe the manifestation. That's why we see all shades of this from a wee bit easier to break when skiing to in utero lethal.