Author Identifiers

Georgios Mavropalias
ORCID: 0000-0001-7753-5693

Date of Award


Degree Type


Degree Name

Doctor of Philosophy


School of Medical & Health Sciences

First Advisor

Professor Ken Nosaka

Second Advisor

Professor Anthony Blazevich


Both the acute damage and resulting adaptations induced by eccentric exercise have been well documented, but less is known about their underpinning mechanisms. It is possible that muscle extracellular matrix (ECM), including both collagenous and costameric (e.g. integrins) components, plays a major role in both damage and adaptation, but this has not been extensively investigated. Eccentric cycling (ECC) was chosen as a model to investigate these mechanisms, since it consists only of eccentric muscle actions, and can induce typical characteristics of muscle damage such as prolonged decreases in muscle function and delayed onset muscle soreness (DOMS); while ECC training has been shown to induce increases in muscle function and muscle mass, even at low intensities. The purpose of this PhD project was to investigate the muscle damage and adaptations induced by the ECC in relation to collagen breakdown and integrin signalling pathways, which may shed light on the connection between ECM-mediated muscle changes.

This research project consisted of three studies. In Study 1, high- (HI) and low-intensity (LI) ECC with the same mechanical work were compared for changes in muscle function and DOMS, while the repeated bout effect was examined after subsequent HI ECC. Eleven men performed HI-ECC (1 min × 5 at 20% of peak power output: PPO) for two bouts separated by 2 weeks (H-H), and nine men performed LI-ECC (4 min × 5 at 5% PPO) for the first bout and then HI-ECC for the second bout (L-H). At 24 h after the first bout, both groups showed similar decreases in maximal isometric (70° knee angle, -10.6±11.8%) and isokinetic (-11.0±8.2%) knee extensor (KE) torque, and squat (-7.7±10.4%) and counter-movement (-5.9±8.4%) jump heights (P

In Study 2, plasma CK activity, hydroxyproline (Hyp) and cell-free DNA (cfDNA) concentrations were measured before, immediately after and 24 – 72 h after HI-ECC and LIECC, and examined in relation to changes in maximum voluntary isometric contraction strength (MVIC) and DOMS. The participants were the same as those in Study 1. Plasma CK activity increased at 24 h (135%), and Hyp concentration increased (40–53%, P

In Study 3, changes in the expression of integrin – integrin-linked kinase (ILK) – rapamycin-insensitive companion of mTOR (RICTOR) protein complex in VL before and after 8 weeks of HI-ECC training were examined along with possible associations to changes in muscle function and VL cross-sectional area (CSA) from pre- to post-training. Eleven young men completed 24 sessions of ECC with progressive increases in intensity and duration, resulting in a 2-fold increase in work from the first 3 sessions (75.4±14.1 kJ) to the last 3 sessions (150.7±28.4 kJ). Lower-limb lean mass (dual-energy X-ray absorptiometry), VL CSA (extended field-of-view ultrasonography), lower-limb static strength measured on the ergometer (breaking strength against the force provided by the crank pushing the foot), peak and average cycling power output were measured, and VL micro-biopsy samples were obtained before and after training. Significant (P

The findings from the three studies provide new insights into the mechanisms underlying muscle damage and adaptations induced by eccentric exercise. The Study 1 results showed that even low-intensity eccentric muscle actions affected the ECM, as indicated by DOMS, which has been shown by previous studies to be more associated with connective tissue damage and inflammation. ECC did not induce extensive muscle fibre damage, as indicated by the small increases in plasma CK activity. It is interesting that the increases in plasma Hypconcentration were similar between HI-ECC and LI-ECC, despite a significant difference in DOMS magnitude. ECC training increased integrin-ILK-RICTOR expression, but it was not associated with the increased CSA or muscle function. It seems possible that the ECM is involved in muscle damage and adaptations, but this was not endorsed by the present studies. It is necessary to investigate further histological changes in ECM after the initial and repeated bouts of eccentric exercise, how eccentric exercise induces ECM remodelling, and how this affects changes in muscle architecture including muscle CSA or mass and muscle function.

Access Note

Chapters 2, 3, 4 and 5 are not available in this version of the thesis.

Available for download on Sunday, August 24, 2025