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Mechanobiology: the stress of life

Thursday 20th Feb 2020, 10.00am

We often think of our bodies in terms of cells and genes, but we shouldn’t forget that they’re also complex mechanical structures. From an Achilles tendon – that can carry half the weight of a Mini – to our constantly pulsing blood vessels, they’re feats of meticulous engineering. Scientists at the University of Oxford are showing how research at the interface of biology and mechanical engineering can lead to exciting new therapies, for example in the treatment of osteoporosis and high blood pressure.

Mechanobiology: the stress of life

Beyond cells and genes...

Advancements in our knowledge of how cells and genes work has been a crucial leap forward in our understanding of the human body, revolutionising medicine in the 21st Century. However, you might be so used thinking of the body in that way, that you don’t think of it as a mechanical system.

But actually, you probably have direct experience of the mechanics of your body – you might have broken a bone, sprained a joint, or pulled a muscle. Or you might know someone – perhaps an older relative or friend – who has a joint replacement or a prosthetic heart valve. Mechanical thinking applied to the body has ancient roots, is widespread, and is vital when it comes to devising the new interventions and therapies we need for healthy and high quality living in the 21st century.

 

The body is a complex mechanical structure.

 

Mechanical thinking applied to the body has ancient roots.

Ancient roots

Aristotle understood the bodies of animals and humans as mechanical systems with movement driven by muscular contraction. Leonardo da Vinci, Giovanni Borelli and others developing the new science of mechanics naturally applied it to the study of human and animal bodies as their writing and sketches of anatomy-inspired machines show. Mechanical thinking at whole body, organ and cell scale still underlies many of the basic concepts in our anatomy and physiology textbooks. However, our rapid leaps forward in biology have led us to forget the fundamental role of mechanics.

Mechanobiology is the new insight that the field of mechanics is crucial for understanding living systems, alongside genetics, proteomics and other breakthrough biological sciences. Mechanical stress (a measure of how much something is loaded) and mechanical strain (a measure of how much it has changed shape) are essential for a full explanation of how life works.

 

Scientists looking at the mechanics of the body.

 

This insight underlies three key concepts for current biomedical research:

Mechanobiology is crucial for understanding living systems.

Tissues need loading for health

The human body experiences mechanical loading every second of every day – our hearts beat, blood rushes along large pulsing arteries, our lungs fill and empty, our muscles contract and relax repeatedly. Any materials carrying such repeated stresses suffer a process known as fatigue – microscopic cracks slowly grow longer and other damage gradually accumulates. In engineering, materials’ catastrophic failure may occur if the problem is not identified and repaired – this is why aircraft and bridges are subject to regular inspection and critical components are replaced after a set time.

                                                                                                  

Cartoon of a beating heart.

 

Many of the living materials in the human body are able to sense and repair mechanical microdamage on an ongoing basis (note that this repair is very different from the healing process that occurs after an injury). This allows the “homeostasis” or maintenance of the tissue. This process of homeostasis enables tissues such as bone and muscle to adapt to changing patterns of use. Higher levels of mechanical stress can strengthen the tissue. This effect is seen in the forearms of professional tennis players, where the bones are stiffer and denser in their serving, compared with non-serving, forearm (Krahl et al 1995). Conversely, reduced levels of loading result in weaker, less stiff tissue. This concerns astronauts spending extended time in microgravity on the International Space Station who experience dramatic bone and muscle loss even when they follow specially designed exercise programmes (Sibonga et al 2015).

 

Exercise can increase bone density.

 

We know little about the homeostatic repair processes in other tissues. For example tendons like the Achilles are frequently heavily loaded with more than five times body weight or “half a Mini” (Komi 1990), and yet rupture is rare.

Understanding how tissues stay healthy under normal, everyday (yet challenging) repeated mechanical loading will give insights into many diseases. It will also inspire the engineering of self-healing materials for safety-critical structures in bridges and aeroplanes.

The Achilles tendon can carry half the weight of a Mini!

In vitro models need appropriate mechanical environment

In vitro (from the Latin meaning in glass) models allow the study of living cells and tissue in the laboratory. In vitro models are essential for reducing the use of animals in research. Pharmaceutical companies use in vitro models to assist in screening new drugs, and in vitro models are key in developing tissue engineering therapies.

Cells can be cultured on the surface of dishes and such “2D” models have been used in experiments for decades. However it is well-known that cells are highly sensitive to their mechanical environment. This means that cells grown on stiff plastic can be very different from cells grown in a 3D scaffold or on a soft gel. Given appropriate mechanical cues, cells can spontaneously align and produce organised tissue, for example contractile muscle (Khodabukus et al 2018).

Mechanobiology is essential in the design of an in vitro models’ mechanical “environment” so that the biology of the model accurately reflects the biology of the tissue in the patient.

 

Mechanobiologist in the lab.

In vitro models are key in developing tissue engineering therapies.

Modulating mechanobiology for therapy

Mechanobiology provides new tools for intervening in physiology for new therapies. For example, this can be external mechanical loading which is used to treat the bone loss disease osteoporosis. A vibrating platform (Marodyne LiV) may slow the rate of bone loss in these patients (Ozcivici et al 2010). Devices for fixing broken bones must be precisely designed to provide appropriate mechanical loading (not too much and not too little) for the healing bone. Tendon repair patches (Biopatch) are engineered to provide precisely calibrated support to the healing tissue.

Since tissue mechanical homeostasis is so fundamental to tissue health, mechanobiology may also be used to identify biological pathways that may be targeted with new drugs to combat disease and damage. Mechanobiological drugs already in use include Angiotensin Converting Enzyme (ACE) inhibitors that relax the blood vessels in treatment for high blood pressure.

 

Mechanobiological drugs are already in use...

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