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Editorial

Mechanobiology in Medical Diagnostics and Therapy PUBLIC ACCESS

[+] Author and Article Information
Chun Y. Seow

Department of Pathology and Laboratory Medicine,
University of British Columbia,
Vancouver, BC V6Z 1Y6, Canada

Ahmed M. Al-Jumaily

Institute of Biomedical Technologies,
Auckland University of Technology,
Auckland 1010, New Zealand

ASME J of Medical Diagnostics 1(2), 020201 (Mar 21, 2018) (2 pages) Paper No: JESMDT-18-1014; doi: 10.1115/1.4039559 History: Received March 06, 2018; Revised March 08, 2018
FIGURES IN THIS ARTICLE

Understanding the influence of stress and strain on biological processes and the properties of biological materials is crucial in unraveling biological mechanisms. This insight came early for muscle physiologists, which is not surprising because they were dealing with a tissue whose function is primarily mechanical in nature. Archibald Hill, a mathematician turned physiologist, first described the relationship between shortening velocity of skeletal muscle as a function of load, and how the relationship was altered by the underlying chemical reactions which manifested themselves as heat production [1]. The hyperbolic force–velocity relationship of muscle contraction was later shown to be the consequence of the interaction between two contractile proteins, actin and myosin, under the physical constraint of a sarcomeric structure [2]. The stochastic process governing the cyclic interaction between actin and myosin is a classic example of mechanobiology where the rate of a chemical reaction (e.g., hydrolysis of adenosine triphosphate (ATP)) is controlled by mechanical strain on the myosin molecules, and the transition between two mechanical states (i.e., detachment of myosin from actin) is controlled by a chemical reaction (release of adenosine diphosphate (ADP) from, and binding of ATP to, myosin) [3]. The stochastic steps within the cross-bridge cycle represent a complex mechanobiochemical process that allow the muscle to contract and ensure the contraction to proceed at maximal efficiency [4]. Muscle, like many biological systems, is a machine that converts energy to mechanical work; we might liken this process to an internal combustion engine that uses gasoline to produce work. Understanding only the biochemistry of ATP hydrolysis without understanding the mechanical cross-bridge cycle to which the chemical reaction is coupled is akin to understanding the chemistry behind the burning of gasoline in open air and not understanding the burning of gasoline in an internal combustion engine.

Physiological insights derived from muscle research have led to useful practical applications, especially in the design of human-powered mechanical devices. A good example is the gear-system of a bicycle which allows variable peddling speeds and optimizes power output. This of course is based on Hill's force–velocity relationship for skeletal muscle [1], which indicates that the muscle's maximal power output occurs when the muscle is working against a load that is approximately one-third of the maximal force the muscle can generate.

The need for putting mechanobiology (and subclassifications such as mechanobiochemistry and mechanopharmacology) into a distinct category stems from the fact that many organs (such as the heart and lung) in our bodies are constantly in motion from birth until death, and that many of the cells and tissues from these organs behave differently under static or dynamic conditions. Unfortunately, even today the majority of biochemical and pharmacological studies are carried out under static conditions only, without taking into account the normal in vivo physiological state of the tissue or cells being studied. For example, many of the smooth muscle pharmacology laboratories investigating drug–receptor interactions are only equipped with force transducers capable of measuring isometric force. Increasingly, it has been shown that tissues or cells under dynamic stress and strain behave differently in their in vivo environments to static conditions [5]. In airway smooth muscle, it has been shown that cyclic stress synergistically facilitates the relaxant effect of bronchodilators [6], possibly due to the bronchodilator-induced reduction in muscle stiffness which allows the same stress to cause a greater strain, and this in turn leads to more strain-induced relaxation [7]. Excessive stiffening of arterial and airway smooth muscle could lead to pathological conditions because it diminishes stress-induced muscle relaxation [8]. Smooth muscle stiffness is therefore a potential target for medical intervention [9,10]. Muscle stiffness can be reduced through pharmacological (e.g., the use of bronchodilators) or mechanical (e.g., stress oscillations) interventions or a combination of both (mechanopharmacological intervention). For example, recent studies have demonstrated promising results in treating obstructive airway diseases using intrapulmonary pressure oscillations [11,12].

Translation of biological insights into useful applications should be one of the most important tasks for biomedical engineers. Although this editorial is mostly about mechanobiology, it should be clear that any biological insight could inspire translational research in any field of engineering. Translation of insights from multidisciplinary research into diagnostic or therapeutic devices or procedures will undoubtedly be a fruitful area of research, especially when the research is conducted by a collaborative team of engineers and medical and clinical scientists. The ASME Journal of Engineering and Science in Medical Diagnostics and Therapy recognizes the importance of translational research and acknowledges that such research is best carried out through collaborative approaches based on applied and basic sciences. One of the goals for this new journal is to provide a platform that is open, efficient, and responsive to the needs of individuals or teams of investigators involved in medical translational fields of research. It aims to encourage participation of researchers from both engineering and medical sciences by making the articles published in this journal readable to members from both communities. Engineering knowledge and perspectives are essential in solving healthcare challenges. The journal strives for moving research from bench to bedside by integrating engineering approaches with clinical needs and by maximizing the exposure of knowledge from this area of translational research to the most relevant readers.

References

Hill, A. V. , 1938, “The Heat of Shortening and the Dynamic Constants of Muscle,” Proc. R. Soc. London B, 126(843), pp. 136–195. [CrossRef]
Huxley, A. F. , 1957, “Muscle Structure and Theory of Contraction,” Prog. Biophys. Biophys. Chem., 7, pp. 255–318. https://bio.ph.tum.de/fileadmin/user_upload/Vorlesungsmaterial/ZellBiochem/Huxley_PBB1957.pdf [PubMed]
Lymn, R. W. , and Taylor, E. W. , 1971, “Mechanism of Adenosine Triphosphate Hydrolysis by Actomyosin,” Biochemistry, 10(25), pp. 4617–4624. [CrossRef] [PubMed]
Eisenberg, E. , and Hill, T. L. , 1985, “Muscle Contraction and Free Energy Transduction in Biological Systems,” Science, 227(4690), pp. 999–1006. [CrossRef] [PubMed]
Krishnan, R. , Park, J. A. , Seow, C. Y. , Lee, P. V. , and Stewart, A. G. , 2016, “Cellular Biomechanics in Drug Screening and Evaluation: Mechanopharmacology,” Trends Pharmacol. Sci., 37(2), pp. 87–100. [CrossRef] [PubMed]
Ansell, T. K. , Noble, P. B. , Mitchell, H. W. , and McFawn, P. K. , 2014, “Pharmacological Bronchodilation is Partially Mediated by Reduced Airway Wall Stiffness,” Br. J. Pharmacol., 171(19), pp. 4376–4384. [CrossRef] [PubMed]
Fredberg, J. J. , Inouye, D. S. , Mijailovich, S. M. , and Butler, J. P. , 1999, “Perturbed Equilibrium of Myosin Binding in Airway Smooth Muscle and Its Implications in Bronchospasm,” Am. J. Respir. Crit. Care Med., 159(3), pp. 959–967. [CrossRef] [PubMed]
Gunst, S. J. , and Fredberg, J. J. , 2003, “The First Three Minutes: Smooth Muscle Contraction, Cytoskeletal Events, and Soft Glasses,” J. Appl. Physiol., 95(1), pp. 413–425. [CrossRef] [PubMed]
Raqeeb, A. , Jiao, Y. , Syyong, H. T. , Paré, P. D. , and Seow, C. Y. , 2012, “Regulatable Stiffness in Relaxed Airway Smooth Muscle: A Target for Asthma Treatment?,” J. Appl. Physiol., 112(3), pp. 337–346. [CrossRef] [PubMed]
Seow, C. Y. , 2013, “Passive Stiffness of Airway Smooth Muscle: The Next Target for Improving Airway Distensibility and Treatment for Asthma?,” Pulm. Pharmacol. Ther., 26(1), pp. 37–41. [CrossRef] [PubMed]
Haba-Rubio, J. , Petitpierre, N. J. , Cornette, F. , Tobback, N. , Vat, S. , Giallourou, T. , Al-Jumaily, A. , and Heinzer, R. , 2015, “Oscillating Positive Airway Pressure Versus CPAP for the Treatment of Obstructive Sleep Apnea,” Front. Med., 2, p. 29.
Jo-Avila, M. J. , and Al-Jumaily, A. M. , 2017, “Superimposed Pressure Oscillations: An Alternative to Treat Airway Hyperresponsiveness in an Acute Sensitized Airways Mouse Model,” Respir. Physiol. Neurobiol., 238, pp. 1–6. [CrossRef] [PubMed]
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References

Hill, A. V. , 1938, “The Heat of Shortening and the Dynamic Constants of Muscle,” Proc. R. Soc. London B, 126(843), pp. 136–195. [CrossRef]
Huxley, A. F. , 1957, “Muscle Structure and Theory of Contraction,” Prog. Biophys. Biophys. Chem., 7, pp. 255–318. https://bio.ph.tum.de/fileadmin/user_upload/Vorlesungsmaterial/ZellBiochem/Huxley_PBB1957.pdf [PubMed]
Lymn, R. W. , and Taylor, E. W. , 1971, “Mechanism of Adenosine Triphosphate Hydrolysis by Actomyosin,” Biochemistry, 10(25), pp. 4617–4624. [CrossRef] [PubMed]
Eisenberg, E. , and Hill, T. L. , 1985, “Muscle Contraction and Free Energy Transduction in Biological Systems,” Science, 227(4690), pp. 999–1006. [CrossRef] [PubMed]
Krishnan, R. , Park, J. A. , Seow, C. Y. , Lee, P. V. , and Stewart, A. G. , 2016, “Cellular Biomechanics in Drug Screening and Evaluation: Mechanopharmacology,” Trends Pharmacol. Sci., 37(2), pp. 87–100. [CrossRef] [PubMed]
Ansell, T. K. , Noble, P. B. , Mitchell, H. W. , and McFawn, P. K. , 2014, “Pharmacological Bronchodilation is Partially Mediated by Reduced Airway Wall Stiffness,” Br. J. Pharmacol., 171(19), pp. 4376–4384. [CrossRef] [PubMed]
Fredberg, J. J. , Inouye, D. S. , Mijailovich, S. M. , and Butler, J. P. , 1999, “Perturbed Equilibrium of Myosin Binding in Airway Smooth Muscle and Its Implications in Bronchospasm,” Am. J. Respir. Crit. Care Med., 159(3), pp. 959–967. [CrossRef] [PubMed]
Gunst, S. J. , and Fredberg, J. J. , 2003, “The First Three Minutes: Smooth Muscle Contraction, Cytoskeletal Events, and Soft Glasses,” J. Appl. Physiol., 95(1), pp. 413–425. [CrossRef] [PubMed]
Raqeeb, A. , Jiao, Y. , Syyong, H. T. , Paré, P. D. , and Seow, C. Y. , 2012, “Regulatable Stiffness in Relaxed Airway Smooth Muscle: A Target for Asthma Treatment?,” J. Appl. Physiol., 112(3), pp. 337–346. [CrossRef] [PubMed]
Seow, C. Y. , 2013, “Passive Stiffness of Airway Smooth Muscle: The Next Target for Improving Airway Distensibility and Treatment for Asthma?,” Pulm. Pharmacol. Ther., 26(1), pp. 37–41. [CrossRef] [PubMed]
Haba-Rubio, J. , Petitpierre, N. J. , Cornette, F. , Tobback, N. , Vat, S. , Giallourou, T. , Al-Jumaily, A. , and Heinzer, R. , 2015, “Oscillating Positive Airway Pressure Versus CPAP for the Treatment of Obstructive Sleep Apnea,” Front. Med., 2, p. 29.
Jo-Avila, M. J. , and Al-Jumaily, A. M. , 2017, “Superimposed Pressure Oscillations: An Alternative to Treat Airway Hyperresponsiveness in an Acute Sensitized Airways Mouse Model,” Respir. Physiol. Neurobiol., 238, pp. 1–6. [CrossRef] [PubMed]

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