The Butterfield Lab

A Muscle Mechanics Laboratory

Our laboratory focuses on the mechanical and physiological properties of muscle tissue during in-vivo ambulation and exercise in a number of models.  We collect direct, real time measurements of mechanical properties and performance of skeletal muscle during modified use, and measure the cellular responses thereafter.  Although it is known that muscle adapts following various modes of exercise, the mechanisms that govern these adaptive processes remain unknown at the cellular level and appear to be related to the mechanical micro-environment of individual fibers within the matrix of skeletal muscle.  The additional contributions of altered muscle function to bone and joint health is of great clinical interest, and we have devised new methodologies to further our understanding of the impact of abnormal muscle function on bone, cartilage, and ligament health during exercise

Skeletal muscle tissue is the only tissue in the body that voluntarily contracts. Essential for living, skeletal muscle allows us to preform gross movements such as giving someone a high-five, or the fine motor movements required to become a skilled pianist.  Additionally, skeletal muscle makes up a large amount of your body mass (upwards of 80%) therefore, it plays a huge role in other realms of physiology such as energetics/metabolism, endocrine signalling, and even the immune response.  So if you think muscle is as cool as we do, read further to learn more about the mechanics of the unique scaffolding that make this all possible.  And please feel free to check back on occasion to keep up with our work!

 

Basic Mechanical Structures in Skeletal Muscle

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This figure depicts actin globules combining to form the helical structure of actin, aka the thin filament.  Wrapped around the filament is tropomyosin, a regulatory structure that either 'hides' or exposes the binding sites.  Tropomyosin is anchored by troponin consisting of three isoforms: Troponin T, C, and I.  Troponin T has an affinity for tropomyosin (causing these to bind), troponin I binds to acting, and troponin C binds to Calcium.  When calcium floods the system following an action potential (signal from the nerve) calcium binds to Troponin C and causes a conformational change in the structure allowing the tropomyosin to slide out of the way of actin binding sites.  This allows for the myosin head (thick filament) (which has a strong affinity for actin) to attach and undergo a power stroke- the most basic part of a contraction.

Credit: respiratoryresearch.com

Credit: respiratoryresearch.com

Above is a both a figure and actual image of a sarcomere- the basic contractile unit of muscle. Here we can see the alignment of the thick and thin filaments, anchoring Z-disks (dark black bands), a couple T-tubules, and even a few mitochondria.  Each light and dark region of the sarcomere is defined by its make up of either actin (light I bands), or myosin (dark A bands).  A third filament depicted in the top figure is Titin.  Titin is the biggest protein known to man- so big it took us a while to actually detect it.  Titin is a fascinating element of skeletal muscle that largely governs passive tension. It is anchored at the Z-disk and then actually feeds through the center of the thick myosin filament stabilizing it in space. Recently, it has been hypothesized that titin also may anchor to the thin actin filament likely effecting force enhancement on the descending limb of the Force/Length relationship (more to come). 

Credit: teachmeanatomy.info  

Credit: teachmeanatomy.info

 

The above figure describes what is known as cross-bridge cycling.  The basic mechanical process of muscle contraction.  It is easier to describe if we start at a state of rigor (attachment of myosin and actin) depicted in Step 3. When the energy source ATP attaches to the myosin head, a conformation change takes place at the myosin head, causing it to detach from actin (Step 4).  As the head detaches, ATP hydrolyzes in to ADP and inorganic Phosphate (Step 1).  If calcium enters the system and makes binding sites on actin available, the myosin head will extend and attach to the thin filament.  At this time and inorganic phosophate is released (Step 2), allowing the myosin head to undergo a power stroke moving pulling the actin filament towards the center of the sarcomere (Step 3). Numerous myosin heads preforming this cyclically many times over causes the sarcomere to shorten.  If this happens in series, across and entire muscle, the muscle will shorten producing force.

Basic Properties of Skeletal Muscle Contraction

Credit: faculty.pasadena.edu

Credit: faculty.pasadena.edu

The figure above is referred to as the force length relationship in skeletal muscle or FLR. This is a depiction of force production in relation to the length of a single sarcomere.  It is important to note that this is a static diagram obtained from isometric contractions.  A dynamic contraction would look slightly different, and even more so at the whole muscle level.  Highlighted in red (a) is what is referred to as the plateau region.  This region is the optimal length in which a sarcomere has the optimal overlap of actin and myosin crossbridges.  At this length each myosin head has an equal opportunity of becoming bound to an actin site, undergoing power stroke, and therefore creating the maximal force for this sarcomere.  Moving down to (c) the sarcomere is now what is called the ascending limb of the FLR.  At this point the actin thin filaments begin to come into contact with each other, and the sarcomere is now at a shorter length.  Because the actin has made its way into the H zone (area of the sarcomere where there are no myosin heads) these binding sites can no longer be bound to myosin- therefore decreasing the number of potential crossbridges, and thereby decreasing force production.  Further down the ascending limb (d) the sarcomere continues to shorten to the point in which actin actually begins to over lap- this also impedes crossbrigde formation and at this length it is very difficult to produce a significant amount of force.  Site (b) opposite from the ascending limb is referred to as the descending limb of the force length relationship. When the sarcomere is stretched to longer lengths, the actin and myosin become further and further apart, making the formation of crossbridges very difficult as the myosin and actin cannot come in contact with one another. Once the sarcomere is stretched beyond overlap, it is very difficult to achieve active force production.

Conceptually, we can expand this concept to a whole muscle contraction.  For example: A biceps curl. Working backwards on the FLR lets say you begin to lift a 35lb dumbbell at the gym with your arm completely extended.  With your arm extended your biceps would be at a longer length- therefore you would be starting on the descending limb of the force length relationship.  Think about how much harder it is to over come the weight of the dumbbell and begin to curl up towards your shoulder.  This is because you have little overlap of actin and myosin, therefore it is more difficult to form the crossbridges needed for force production.  However, lets say this 35lb dumbbell is pretty heavy and before you can complete the entire curl you stop to take a break.  More than likely you would stop almost half way, with your elbow at a 90 degree angle.  Here at this range of motion, you might be able to hold on to the dumbbell for quite some time without tiring.  This is because at this point in your curl you have reached the plateau- the optimal length for crossbrigde formation.  Once your break is over, finish your curl and once you reach the end of the motion you may notice once again that it is slightly harder to produce force (one because your forearm and bicep have likely approximated) but also because your sarcomeres are now working on the ascending limb and are running out of room to form the appropriate crossbridges needed for force production.  Mechanics are fun, aren't they :-)