Broadening the approach of studying skinned cardiac muscle

Muscles excised can be ‘skinned’ chemically, enzymatically or mechanically. Skinning removes the cell membrane, either partially or completely, depending on the methods. In either case, skinning dissolves the cell membrane but leaving the internal structure intact. Specifically, the contractile proteins (consist of actin, myosin and the myofilament proteins) remains intact and are studied to understand the contractile properties of cardiac muscle in a more controlled environment. While this allows for detailed study of the molecular mechanisms of contraction, it does not capture the contraction pattern like that achieved using intact (unskinned) muscles. For example, skinned muscles are activated to undergo contracture (sustained contraction), and due to the lack of several other key regulatory proteins, skinned muscles are not subjected to twitch-by-twitch force-length work-loop contractions that emulate the beat-by-beat pressure-volume loop contraction pattern of the heart in vivo.

Such a major limitation of skinned muscle preparations is elaborated when a research institute receives frozen (cryopreserved) cardiac muscle samples from biobanks, i.e., from the Sydney Heart Bank, the UK Cardiovascular Biorepository, etc. These muscle samples when received are then skinned, as these cryopreserved muscles are no longer available as for intact muscle study. Can we predict, justifiably, the work-loop contraction performance of the intact muscle by studying the contractile proteins of the skinned muscle? We have developed increased understanding of the mechanical differences between intact versus skinned muscle, in particular, skinned muscles have a relatively lower sensitivity to Ca2+ and a lower passive force compared with intact muscles. Can these differences when built into a mathematical model be capitalised on to more accurately predict the intact muscle mechanoenergetics?

• Bachelor in Biomedical Engineering or equivalent
  

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