How your cells react to strength or endurance training

When you pick up a dumbbell and do a bicep curl, for example, your body feels it at a molecular level. The dumbbell or the external resistance causes a variety of mechanical stresses, such as shear and tensile forces, on your cells. In cell biology, this is also referred to as mechanosensing [14]. Our tissue and cells are interconnected by different structures. A distinction is made between extracellular and intracellular structures and components.

The extracellular environment of our muscle cells consists largely of collagen. Proteins such as laminin or perlecan bind to it, which in turn are directly connected to internal muscle cell proteins via integrin or dystroglycan. These internal proteins have wonderful-sounding names such as paxilin, talin, vinculin, dystrophin, alpha-actinin and many more. For the interested reader, I refer here to Mavropalias et al, 2022 [15]. If, as mentioned above, external forces act, these are transmitted via structural proteins to the cell interior, where they trigger signals (cell signalling) via biochemical reactions, which ultimately end up in the cell nucleus [16-18]. There, genes are read and the corresponding proteins are translated. The cell can thus react to external stressors.

Any type of force development for exercise or sport is associated with energy consumption and can influence the metabolism of our cells. The disruption of metabolic processes does not go undetected within the cells. In the muscle cell, it is the AMP-activated protein kinase (AMPK) that detects an increase in energy metabolism. It measures the ratio of adenosine triphosphate (ATP) to diphosphate (ADP) or monophosphate (AMP). ATP is the energy currency in our muscle cells. When a phosphate group is split off, energy is produced that the muscles need, among other things, for muscle contraction. The splitting off of a phosphate group leads to a reduction in the number of phosphates in ATP. When a phosphate group is split off, ATP becomes ADP and when another phosphate group is split off from ADP, AMP is formed. AMPK therefore recognises energy stress and coordinates processes in the cell that build up or break down [19].

Energy stress stimulates a signalling pathway with the long English name peroxisome proliferator activated receptor gamma coactivator-1α (PGC-1α), which promotes the formation of mitochondria and blood vessels. Mechanical stress stimulates a signalling pathway via mTOR. This is the abbreviation for mechanistic target of rapamycin and is a signalling pathway that stimulates growth processes such as muscle growth.

Adaptations for endurance and strength training

Endurance training is usually characterised by continuous low-intensity phases [20] that allow the exercises to be maintained over a longer period of time. Typical endurance exercises include walking, running, cycling or swimming. Endurance training poses a challenge to the metabolic system as it disrupts the intracellular concentrations of oxygen, lactate, reactive oxygen species, adenosine triphosphate and calcium [21].
In contrast to endurance training, strength training involves short phases of higher to maximum intensity [22]. Strength training challenges the mechanical integrity [23,24] of the tissue and the metabolic balance of the muscles [25,26]. Systematic application of mechanical [27-29] and metabolic loads [30-32] to the human body results in morphological and neural adaptations [33]. These adaptations include, for example, changes in the size [34,35] and structure [36] of muscle cells, growth of myofibrils and proliferation of mitochondria [37,38], metabolic profiles [39] and much more.

The adaptations of endurance and strength training are different and therefore suggest that differences in the contractile activity of the muscles lead to different adaptations.

As early as 1997, Dolmetsch et al. [40] showed that different signalling pathways are selectively activated depending on the intensity of a signal. Atherton and colleagues isolated muscles from rats in 2005 and stimulated them electrically at a high frequency over a short period of time (6 x 10 repetitions consisting of 3-s bursts of 100 Hz) to simulate strength training or at a low frequency (3 h at 10 Hz) to simulate endurance training. Strength training significantly increased muscle protein synthesis by a factor of 5.3 (P < 0.05) 3 h after stimulation compared to endurance training. The endurance training did not statistically significantly increase the muscle protein synthesis rate compared to the control group. However, the endurance protocol significantly (P < 0.05) increased AMPK activity in the muscle cells after 3 hours and after 6 hours compared to strength training. This led to a significant activation of PGC-1α immediately after training (P < 0.5). Different intensities, simulating endurance or strength training, therefore led to the activation of different signalling pathways. These appear to inhibit each other.

Fascinating how cells can react very sensitively to external stress. This also explains why the adaptations are always very specific to the corresponding training stimulus. Congratulations if you've read this far.

As a little mental exercise, I will now ask the question:

References

Sources 1-13 refer to the info box, sources 14-40 to the body text

1. Wickstead B, Gull K, Richards TA. Patterns of kinesin evolution reveal a complex ancestral eukaryote with a multifunctional cytoskeleton. BMC Evol Biol. 2010;10. doi:10.1186/1471-2148-10-110
2. Hoyt MA, Hyman AA, Bähler M. Motor proteins of the eukaryotic cytoskeleton. Proc Natl Acad Sci U S A. 1997;94: 12747-12748. doi:10.1073/pnas.94.24.12747
3. Hartman MA, Spudich JA. The myosin superfamily at a glance. J Cell Sci. 2012;125: 1627-1632. doi:10.1242/jcs.094300
4. Svitkina T. The actin cytoskeleton and actin-based motility. Cold Spring Harb Perspect Biol. 2018;10: 1-22. doi:10.1101/cshperspect.a018267
5. Vale RD. The molecular motor toolbox for intracellular transport. Cell. 2003;112: 467-480. doi:10.1016/S0092-8674(03)00111-9
6. Barlan K, Gelfand VI. Microtubule-based transport and the distribution, tethering, and organisation of organelles. Cold Spring Harb Perspect Biol. 2017;9: 1-12. doi:10.1101/cshperspect.a025817
7. Cheng F, Eriksson JE. Intermediate filaments and the regulation of cell motility during regeneration and wound healing. Cold Spring Harb Perspect Biol. 2017;9: 1-14. doi:10.1101/cshperspect.a022046
8. Sweeney HL, Hammers DW. Muscle Contraction. J Physiol. 1995;487: 151-165. doi:10.1113/jphysiol.1995.sp020931
9. Geeves MA, Holmes KC. The molecular mechanism of muscle contraction. Adv Protein Chem. 2005;71: 161-193. doi:10.1016/S0065-3233(04)71005-0
10. Squire J. Special issue: The actin-myosin interaction in muscle: Background and overview. Int J Mol Sci. 2019;20: 1-39. doi:10.3390/ijms20225715
11. Geeves MA. The dynamics of actin and myosin association and the crossbridge model of muscle contraction. Biochem J. 1991;274: 1-14. doi:10.1042/bj2740001
12. Hirasawa T, Kuratani S. Evolution of the muscular system in tetrapod limbs 06 Biological Sciences 0604 Genetics. Zool Lett. Zoological Letters; 2018;4: 1-18. doi:10.1186/s40851-018-0110-2
13. Kollmar M, Mühlhausen S. Myosin repertoire expansion coincides with eukaryotic diversification in the Mesoproterozoic era. BMC Evol Biol. BMC Evolutionary Biology; 2017;17: 1-18. doi:10.1186/s12862-017-1056-2
14. Zuela-Sopilniak N, Lammerding J. Can't handle the stress? Mechanobiology and disease. Trends Mol Med. Elsevier Ltd; 2022;28: 710-725. doi:10.1016/j.molmed.2022.05.010
15. Mavropalias G, Boppart M, Usher KM, Grounds MD, Nosaka K, Blazevich AJ. Exercise builds the scaffold of life: muscle extracellular matrix biomarker responses to physical activity, inactivity, and aging. Biol Rev. John Wiley & Sons, Ltd; 2022; doi:10.1111/BRV.12916
16. Hoppeler H. Molecular networks in skeletal muscle plasticity. J Exp Biol. 2016;219: 205-213. doi:10.1242/jeb.128207
17. Flück M, Hoppeler H. Molecular basis of skeletal muscle plasticity-from gene to form and function. Rev Physiol Biochem Pharmacol. 2003;146: 159-216. doi:10.1007/s10254-002-0004-7
18. Vainshtein A, Sandri M. Signalling pathways that control muscle mass. Int J Mol Sci. MDPI AG; 2020;21: 1-32. doi:10.3390/ijms21134759
19. Mounier R, Théret M, Lantier L, Foretz M, Viollet B. Expanding roles for AMPK in skeletal muscle plasticity. Trends Endocrinol Metab. Elsevier Current Trends; 2015;26: 275-286. doi:10.1016/J.TEM.2015.02.009
20. Coffey VG, Hawley JA. Concurrent exercise training: do opposites distract? J Physiol. 2017;595: 2883-2896. doi:10.1113/JP272270
21. Coffey VG, Hawley JA. The molecular bases of training adaptation. Sport Med. 2007;37: 737-763. doi:10.2165/00007256-200737090-00001
22. Egan B, Zierath JR. Exercise metabolism and the molecular regulation of skeletal muscle adaptation. Cell Metab. Elsevier Inc; 2013;17: 162-184. doi:10.1016/j.cmet.2012.12.012
23. Ingber DE. Tensegrity I. Cell structure and hierarchical systems biology. J Cell Sci. 2003;116: 1157-1173. doi:10.1242/jcs.00359
24. Ingber DE. Tensegrity II. How structural networks influence cellular information processing networks. J Cell Sci. 2003;116: 1397-1408. doi:10.1242/jcs.00360
25. Schoenfeld BJ. Potential mechanisms for a role of metabolic stress in hypertrophic adaptations to resistance training [Internet]. Sports Medicine. Springer; 2013. pp. 179–194. doi:10.1007/s40279-013-0017-1
26. Goto K, Ishii N, Kizuka T, Takamatsu K. The impact of metabolic stress on hormonal responses and muscular adaptations. Med Sci Sports Exerc. 2005;37: 955-963. doi:10.1249/01.mss.0000170470.98084.39
27. Fry AC. The role of resistance exercise intensity on muscle fibre adaptations. Sport Med Springer; 2004;34: 663-679. doi:10.2165/00007256-200434100-00004
28. Goldberg AL, Etlinger JD, Coldspink DF, Jableck C. Mechanism of work-induced hypertrophy of skeletal muscle. Med Sci Sports. United States; 1975;7: 248-261. doi:10.1249/00005768-197500740-00003
29. Rindom E, Kristensen AM, Overgaard K, Vissing K, de Paoli FV. Activation of mTORC1 signalling in rat skeletal muscle is independent of the EC-coupling sequence but dependent on tension per se in a dose-response relationship. Acta Physiol. Blackwell Publishing Ltd; 2019;227. doi:10.1111/apha.13336
30. ROONEY K., HERBERT RD, BALNAVE RJ. Fatigue contributes to the strength training stimulus. Med Sci Sports Exerc. 1994;26.
31. Schott J, McCully K, Rutherford OM. The role of metabolites in strength training - II. short versus long isometric contractions. Eur J Appl Physiol Occup Physiol. 1995;71: 337-341. doi:10.1007/BF00240414
32. Carey Smith R, Rutherford OM. The role of metabolites in strength training - I. A comparison of eccentric and concentric contractions. Eur J Appl Physiol Occup Physiol. Springer-Verlag; 1995;71: 332-336. doi:10.1007/BF00240413
33. Folland JP, Williams AG. The adaptations to strength training: Morphological and neurological contributions to increased strength [Internet]. Sports Medicine. Springer; 2007. pp. 145–168. doi:10.2165/00007256-200737020-00004
34. McDonagh MJN, Davies CTM. Adaptive response of mammalian skeletal muscle to exercise with high loads [Internet]. European Journal of Applied Physiology and Occupational Physiology. Springer-Verlag; 1984. pp. 139–155. doi:10.1007/BF00433384
35. Jones DA, Rutherford OM, Parker DF. Physiological Changes in Skeletal Muscle As a Result of Strength Training. Q J Exp Physiol. 1989;74: 233-256. doi:10.1113/expphysiol.1989.sp003268
36. Franchi M V., Reeves ND, Narici M V. Skeletal muscle remodelling in response to eccentric vs. concentric loading: Morphological, molecular, and metabolic adaptations. Front Physiol. Frontiers; 2017;8: 447. doi:10.3389/fphys.2017.00447
37. MacDougall JD, Elder GCB, Sale DG, Moroz JR, Sutton JR. Effects of strength training and immobilisation on human muscle fibres. Eur J Appl Physiol Occup Physiol. Springer-Verlag; 1980;43: 25-34. doi:10.1007/BF00421352
38. Macdougall JD, Sale DG, Moroz JR, Elder G, Sutton JR, Howald H. Mitochondrial volume density in human skeletal muscle following heavy resistance training. Med Sci Sports. 1979;11: 164-166. available: https://europepmc.org/article/med/158694
39. Zanuso S, Sacchetti M, Sundberg CJ, Orlando G, Benvenuti P, Balducci S. Exercise in type 2 diabetes: Genetic, metabolic and neuromuscular adaptations. A review of the evidence [Internet]. British Journal of Sports Medicine. BMJ Publishing Group; 2017. pp. 1533–1538. doi:10.1136/bjsports-2016-096724
40. Dolmetsch RE, Lewis RS, Goodnow CC, Healy JI. Differential activation of transcription factors induced by Ca2+ response amplitude and duration. Nat 1997 3866627. Nature Publishing Group; 1997;386: 855-858. doi:10.1038/386855a0