Explaining how hypertrophy works using only basic principles of muscle physiology

Hypertrophy is an increase in muscle volume, or mass.

Moreover, since there is little evidence that human muscles enlarge through an increase in the number of muscle fibers, the main way that muscles increase in volume is through an increase in the cylindrical volume of multiple, individual muscle fibers.

So what stimulates individual muscle fibers to increase in volume?

We know that muscle fibers are stimulated to increase in size after they are exposed to a certain level of mechanical loading. This stimulus seems to be detected by mechanoreceptors that are located near to the membrane of each individual muscle cell.

However, many long-term studies exploring the hypertrophic effects of strength training have produced results indicating that mechanical loading may not the only factor that stimulates muscles to grow. This observation has driven researchers to search for other mechanisms, such as metabolic stress or muscle damage, that might also stimulate hypertrophy.

But are such hypotheses really necessary?

Can we instead refer to basic muscle physiology to identify how different training methods alter the level and type of mechanical loading that is experienced by individual muscle fibers?

I think we can.

Basic muscle physiology

There are several important features or relationships in muscle physiology that affect the level of mechanical loading that is experienced by a muscle fiber during a muscular contraction, as follows:

• The size principle
• The force-velocity relationship
• The length-tension relationship
• Fatigue

Each of these phenomena affect the amount and the type of force that a muscle fiber exerts during a muscular contraction. This force must be equal and opposite to the amount of mechanical loading that it experiences, which we already know is a key stimulus for the hypertrophy that occurs.

The size principle

The size principle is the observation that motor units, which are the structures that govern groups of muscle fibers, are recruited by the central nervous system in a set sequence, with larger motor units being recruited to meet the demands of more demanding tasks.

Motor units control different numbers of muscle fibers according to their size, and different motor units also govern muscle fibers with different properties. Those motor units that are recruited first in sequence govern very small numbers (dozens) of muscle fibers that are highly oxidative, while the motor units that are recruited last in sequence govern very large numbers (many thousands) of muscle fibers that are much less oxidative.

Motor units are recruited at specific recruitment (force) thresholds. The recruitment threshold of a motor unit is the level of force that a muscle produces in any muscular contraction at which the muscle fibers of that motor unit are first activated. Motor unit recruitment thresholds can differ between contraction modes (eccentric, isometric, and concentric) and change as a result of fatigue. However, motor units are always recruited in the same order of size, regardless of the contraction mode or any other factor, and the low-threshold motor units always remain switched on at the point when the high-threshold motor units are recruited.

Consequently, in unfatigued conditions, low-threshold motor units, which govern small numbers (dozens) of muscle fibers, are recruited to undertake muscular contractions involving low forces, while high-threshold motor units, which govern large numbers (several thousands) of muscle fibers, are recruited in addition to the already-recruited low-threshold motor units to contribute to high muscle forces. This means that only the (small numbers of) muscle fibers governed by low-threshold motor units experience any mechanical loading at low forces, while the muscle fibers of both low- and high-threshold motor units experience mechanical loading at high forces.

The muscle fibers that are governed by high-threshold motor units are far less oxidative than those that are governed by low-threshold motor units, and are also more responsive to the mechanical stimulus that leads to hypertrophy. This greater responsiveness is probably due to the inverse relationship between oxidative capacity and cross-sectional area of single muscle fibers, which makes it difficult for the highly oxidative (type I or slow twitch) muscle fibers that are governed by the low-threshold motor units to increase in size without becoming dysfunctional.

The exponentially greater number of muscle fibers that are controlled by the high-threshold motor units, and their greater responsiveness to hypertrophy, means that the muscle fibers controlled by high-threshold motor units grow in size substantially more than those controlled by low-threshold motor units. This explains why repeated, unfatiguing contractions at low force levels (e.g. aerobic exercise) does not produce much hypertrophy, while repeated contractions at high force levels (e.g. strength training) does.

The force-velocity relationship

The force-velocity relationship is the observation that muscle fibers produce more force when they are able to shorten slowly, compared to when they shorten quickly.

Muscle fibers produce more force when they shorten slowly because slow shortening velocities allow a greater number of crossbridges to form at the same time between the actin and myosin myofilaments. Slower shortening velocities allow the crossbridges to remain attached for longer, after they are initially formed, which we can measure as a slower detachment rate.

These crossbridges are what generates force within each muscle fiber, so when more of them are attached at the same time, this leads to greater muscle fiber force, and therefore a higher level of mechanical loading. This high level of mechanical loading is what stimulates muscle growth.

Long-term strength training studies have revealed many instances in which the force-velocity relationship can explain the results that are recorded, while the size principle alone cannot.

For example, heavy squats and jump squats with light loads both typically involve high, or even maximal levels of motor unit recruitment. This means that all of the muscle fibers in the muscle are activated during each set of each exercise, including those of the high-threshold motor units that are very responsive to a mechanical loading stimulus. Yet, only heavy strength training programs using squats lead to muscle growth. This can be explained using the force-velocity relationship: slower muscle fiber shortening velocities lead to higher forces being exerted by each of the muscle fibers of the active, high-threshold motor units, which triggers those fibers to increase in size.

The length-tension relationship

The length-tension relationship is the observation that muscle fibers produce more force at certain lengths, compared to at others.

This relationship is a composite of two underlying, separate relationships, which are the active length-tension relationship, and the passive length-tension relationship.

Muscle fibers produce more force when they are lengthened to very long lengths, because of the passive length-tension relationship. This relationship is determined by the elastic properties of the structural elements of the fiber, such as the cell cytoskeleton, large molecules including titin, and the surrounding collagen layer of the fiber, called the endomysium.

Muscle fibers also produce a peak in force when they contract at an optimum length, because of the active length-tension relationship. This relationship is determined by the degree of overlap between the actin and myosin myofilaments.

When the muscle fiber is forcibly lengthened, this places a large mechanical load on its passive elements, which deforms it longitudinally. This stimulates the fiber to grow in a way that meets the demand, which is to increase in length. When the muscle fiber produces a large contractile force with its active elements, it bulges outwards because of the large number of actin-myosin crossbridges that form, which deforms it transversely. This stimulates the fiber to grow in a way that meets the demand, which is to increase in diameter.

Long-term strength training studies have revealed many instances in which the length-tension relationship can explain the results that are recorded.

For example, full range of motion training causes hypertrophy while increasing fascicle length to a greater extent, while partial range of motion training predominantly causes increases in cross-sectional area. This happens because the full range of motion involves stretching the muscle fibers to a greater extent than the partial range of motion. Similarly, eccentric-only and concentric-only strength training produce similar increases in muscle volume, but eccentric-only training mainly increases fascicle length, while concentric-only training mainly increases muscle cross-sectional area. This happens because eccentric-only (lengthening) contractions involve placing a greater stress on the passive elements of the muscle fibers throughout the whole exercise range of motion.

Fatigue

Peripheral fatigue changes the way in which muscle fibers behave in the context of the above basic principles of muscle physiology, which alters the degree of mechanical loading that they experience.

The size principle — Peripheral fatigue changes the recruitment (force) threshold of motor units, although this does not affect the order in which the motor units are recruited. When a muscle is fatigued, the recruitment (force) threshold reduces. So high-threshold motor units are recruited at lower levels of force. This means that when a muscle is very fatigued, it can display a very high level of motor unit recruitment, despite only producing a low level of force. Fatigue therefore contributes to hypertrophy by increasing the number of high-threshold motor units that can be recruited in any given muscular contraction with a submaximal load.

The force-velocity relationship — Peripheral fatigue reduces bar speed, by reducing the contraction velocity of muscle fibers, as well as their ability to produce force. While it is hard to tell whether fatigue allows fatigued muscle fibers to increase the force that they produce at the slower velocity, it certainly causes unfatigued muscle fibers of any newly-recruited motor units to produce greater force, and therefore experience higher levels of mechanical tension because of the force-velocity relationship. Fatigue therefore contributes to hypertrophy by increasing the force that each muscle fiber produces during a submaximal contraction with a light load, by reducing the speed at which the muscle shortens.

The length-tension relationship — Peripheral fatigue changes the maximum amount that muscle fibers lengthen during a lengthening contraction, by reducing their ability to contribute active force. This leads to a greater amount of mechanical loading being placed upon the passive elements of the muscle fibers (which facilitates greater muscle fiber elongation), compared to in unfatigued muscle, which may cause greater longitudinal hypertrophy.

What is the takeaway?

Hypertrophy is the result of individual muscle fibers experiencing mechanical loading and subsequently increasing in volume. The size and the type of the mechanical load that muscle fibers experience is determined by basic muscle physiology, including the size principle, the force-velocity relationship, the length-tension relationship, and fatigue. Consequently, by looking at how basic muscle physiology affects mechanical loading during different types of strength training, it is possible to explain the results of most long-term training studies.