Can passive mechanical tension stimulate increases in muscle fiber cross-sectional area?
For many months, Paul has been telling me that some researchers and fitness influencers are taking the position that passive mechanical tension can stimulate increases in muscle fiber cross-sectional area. At first, I did not believe that anyone would seriously ever make that claim, but it is now becoming too obvious to ignore. In this article, I’m going to show you why that is almost certainly impossible (and not just improbable).
How do muscles grow and how do we measure that?
Animal models
Muscles display hypertrophy when single muscle fibers increase either in their cross-sectional area (by adding myofibrils in parallel) or in length (by adding sarcomeres in series). While an increase in muscle mass can also occur by the addition of new muscle fibers in animal models, this is called hyperplasia and is not considered the same as hypertrophy. In animal models, we can measure hypertrophy directly using dissection methods that allow assessment of the entire muscle and also the individual muscle fibers within it. In such investigations, we end up with a relatively clear understanding of the actual changes that the individual muscle fibers have experienced, both radially and longitudinally.
This feature of animal model measurements is important because it means that we can separate out the stimuli that cause each type of adaptation. For example, if one type of exercise training causes an increase in muscle fiber cross-sectional area but no addition of sarcomeres in series, that tells us something about the unique nature of the stimulus that causes myofibrils to be added (since it is present) and also about the unique nature of the stimulus that causes sarcomeres to be added (since it is absent). On the other hand, if another type of exercise training causes muscle fiber length to increase but does not increase muscle fiber cross-sectional area, that tells us something about the unique nature of the stimulus that causes sarcomeres to be added (since it is present) and about the unique nature of the stimulus that causes myofibrils to be added (since it is absent). In each case, we can look to see what type of stimulus is present and what type of stimulus is absent in order to understand what stimulus is inherent to the exercise that is causing each of the adaptations to happen.
Human studies
In human studies, direct measurements of muscle fiber cross-sectional area and sarcomere number are very rare. Studies have measured changes in single muscle fiber cross-sectional area after strength training programs, but the quality of such measurements is very poor because they necessarily rely upon biopsies, which clearly only reflects a small proportion of the whole muscle. Scientists have also recorded increases in sarcomere number of humans, albeit this is less widely-appreciated and even some researchers are unaware of it. In humans, hypertrophy is most commonly measured at the whole muscle level. Many measurement methods are possible, including muscle volume, anatomical cross-sectional area (ACSA), physiological cross-sectional area (PCSA), and muscle thickness. Moreover, we can also measure architectural changes such as alterations in muscle fascicle length and pennation angle.
In respect of whole muscle measurements, it is challenging to extrapolate to what is occurring at the single muscle fiber level. In the case of muscle fascicle length, many researchers assume that increases or decreases in fascicle length do reflect increases and decreases in sarcomere number. Indeed, this makes sense because these two changes occur in parallel in many animal models (albeit not necessarily perfectly in parallel when using ultrasound to measure the fascicle length changes). Also, muscle fascicle length only increases in response to training methods that involve passive mechanical tension (such as static stretching, strength training at long muscle lengths, and eccentric-only training), which is known to be the same stimulus that causes sarcomerogenesis to happen in animal models (and we do have evidence that sarcomeres increase in number in humans, despite what some researchers will tell you). Nevertheless, in the case of ACSA, PCSA, and muscle thickness, it is impossible to infer that muscle fiber cross-sectional area necessarily increases because an increase in muscle length by means of sarcomere number could easily cause a similar whole muscle size change owing to the geometry of the muscle itself.
Implications
We can use animal models to explore the types of strength training and mechanical loading that produce increases in muscle fiber cross-sectional area or muscle fiber length. However, it is very challenging to use human studies because increases in most whole muscle size measurements can be produced by either increases in muscle fiber cross-sectional area or muscle fiber length. The only main exception to this rule is an increase in muscle fascicle length, which likely reflects an increase in muscle fiber length due to the addition of sarcomeres in series.
What stimulates single muscle fibers to increase in diameter and/or length?
Introduction
There are many different animal models that are useful for understanding basic muscle physiology, when it comes to teasing apart the increases in muscle fiber diameter (through myofibrillar addition) from the increases in muscle fiber length (through sarcomerogenesis). However, the two main ones are limb immobilization and regular static stretching. So let us now work our way through some important studies in those two areas.
Limb immobilization studies
Limb immobilization is a common way of producing increases and decreases in sarcomere number. Typically, the number of sarcomeres in an immobilized muscle increases when limbs are immobilized at long muscle lengths, and decreases when they are immobilized at short muscle lengths. Importantly, research typically shows that when an increase in muscle weight occurs after immobilization at a long muscle length, this can be explained entirely by the addition of new sarcomeres, which implies that there is no simultaneous myofibrillar addition. Evidently, this tells us that when passive mechanical tension is applied by the stretching of structures inside the muscle fiber but without the simultaneous application of active mechanical tension due to actin-myosin crossbridge formations, this only stimulates the addition of sarcomeres and not the addition of myofibrils. Taking things one step further, limb immobilization often causes a loss of muscle mass and PCSA. Nevertheless, when limbs are immobilized at long muscle lengths, there is still an increase in the number of sarcomeres in series despite the disuse atrophy. Evidently, this tells us that the stimulus for sarcomerogenesis is totally separate from the stimulus for myofibrillar addition, since one adaptation is growing while the other is shrinking.
Summary: when limbs are immobilized at a long length, sarcomeres are added in series even though muscle fiber cross-sectional area either does not increase or even decreases. This shows that the stimulus for adding sarcomeres in series is totally different from the stimulus for adding myofibrils in parallel.
Static stretching studies
Static stretching (usually daily or at least several times per week) is yet another common way of producing increases in sarcomere number. Often, static stretching is performed in healthy, untrained muscle but sometimes it is applied in the recovery process after disuse atrophy or following limb immobilization. In such cases, the amount of sarcomerogenesis is usually greater because the starting point is abnormally low. Obviously, this makes the identification of changes easier to achieve. Nevertheless, research has shown that when static stretching is applied during such recovery periods, it stimulates a rapid increase in sarcomeres in series without any increase in muscle fiber cross-sectional area, despite the extremely detrained state of the target muscle, which would be expected to respond very strongly to any relevant stimulus. Taking one step further, static stretching has been shown to create an increase in the number of sarcomeres in series while muscle fiber cross-sectional area simultaneously decreases. Again, this tells us that sarcomere addition and myofibrillar addition are separate adaptations, since one can increase while the other can decrease.
Summary: when limbs are statically stretched, sarcomeres are added in series even though muscle fiber cross-sectional area either does not increase or even decreases. This shows that the stimulus for adding sarcomeres in series is totally different from the stimulus for adding myofibrils in parallel.
Mechanism of sarcomerogenesis
From the studies described above, we can see that passive mechanical tension applied in the absence of active mechanical tension can cause sarcomere addition even while myofibrils are lost due to atrophy. This is incredibly important because it makes it impossible to claim that passive mechanical tension increases muscle fiber cross-sectional area (which is an unnecessary hypothesis anyway, because any extra increases in whole muscle size such as changes in anatomical cross-sectional area or muscle thickness after stretch-type training can easily be attributed to increases in sarcomeres in series).
We know from many decades of sarcomerogenesis research (especially the distraction studies) that the lengthening of sarcomeres past a certain key threshold is the stimulus for adding sarcomeres in series. Research in other fields has made the observation that muscle fiber strains are needed, but this is only true so long as sufficient sarcomere elongation occurs because of the muscle fiber strain. Ultimately, a sarcomere must be elongated past a certain point for enough passive mechanical tension to be produced by way of the stretching of the stiff segment of titin. Indeed, when titin molecules are modified to be shorter (and therefore stiffer) in mouse strains, the mice display hypertrophy by means of sarcomerogenesis. This is a very strong mechanistic basis upon which to build our understanding of what causes sarcomeres to be added during exercise.
Summary: the lengthening of sarcomeres past a certain key threshold is the stimulus for adding sarcomeres in series because it produces passive mechanical tension by the stretching of the stiff segment of titin. This stimulus does not cause any addition of myofibrils in parallel.
Mechanism of myofibrillar addition
From the studies described above, we can see that passive mechanical tension does not cause an increase in muscle fiber cross-sectional area due to an increase in myofibrils. However, we know that strength training does achieve that. We know that mechanical tension can be generated by activating a muscle fiber such that it forms actin-myosin crossbridges. When enough crossbridges are formed simultaneously (which occurs at slow muscle fiber shortening speeds), this generates a sufficiently high level of active mechanical tension to stimulate the addition of myofibrils in parallel, while insufficient crossbridge formation (which occurs at faster muscle fiber shortening speeds) does not. This is what happens during most types of strength training. We can see it happening in animals when muscle fiber cross-sectional area increases without sarcomere addition, and we can see it happening in humans when whole muscle size increases without muscle fascicle length changes.
N.B. While we do not have direct evidence of it happening, it is extremely likely that sarcomeres in series can be lost while myofibrils in parallel are added, for example during programs of isometric training at short muscle lengths or during programs of partial range of motion or concentric-only strength training. They are lost during aerobic exercise involving partial ranges of motion with peak forces at short muscle lengths. And of course, we know that torque-angle curves are altered to permit length-tension plateaus to occur at shorter muscle lengths following such strength training programs. This reinforces our understanding that the stimulus that causes the addition of sarcomeres in series must necessarily be completely independent of the stimulus that causes an increase of myofibrils in parallel.
Summary: the generation of active mechanical tension above a certain key threshold by the formation of actin-myosin crossbridges is the stimulus for adding myofibrils in parallel. This stimulus does not produce the addition of any sarcomeres in series.
What is the conclusion?
Muscle fibers can increase in diameter. This occurs by the addition of myofibrils in parallel. Muscle fibers can also increase in length. This occurs by the addition of sarcomeres in series. Both of these adaptations can contribute to increases in whole muscle size and mass. Yet, there is very clear evidence showing that these two adaptations are completely separate from one another such that one can occur while the other does not (or even dissipates). When limbs are immobilized at a long length or statically stretched, sarcomeres are added in series even though muscle fiber cross-sectional area either does not increase or even decreases. Such findings show that the stimulus for adding sarcomeres in series is totally different from the stimulus for adding myofibrils in parallel. Therefore, we should not expect passive mechanical tension to stimulate the addition of myofibrils in either static stretching programs or during strength training at long muscle lengths.
