Electron Tomography of Muscle Sarcomere

Laboratory of Pradeep Luther, PhD

National Heart & Lung Institute, Faculty of Medicine, Imperial College London.

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Group Leader

Dr Pradeep Luther

 

 

April 2023

2 New papers in Journal of Muscle Research and Cell Motility.

 

Dec 2021

New paper in Journal of Royal Society Interface.

Images from the lab (click to enlarge)

 

Contents of this site, text and photographs are copyright of Pradeep Luther except where stated otherwise.

 

Last modified 10may2023

 

Welcome to the Sarcomere Structure website.  Our goal is to understand the complete structure of the striated muscle sarcomere and to relate the structure to how it works.   This website illustrates what we do.

 

In our body we have smooth muscle that lines our guts and arteries, and we have striated muscle which powers our heart (cardiac muscle) and lines our limbs and our frame (skeletal muscle).  The striated appearance is clearly seen when a thin muscle is viewed under a microscope (click here).  Striated muscles produce movement in every animal.  The sarcomere is the repeating unit of striated muscle.   Thus to understand how muscles work, we need to understand the structure and function of a single sarcomere.

 

Muscle contraction occurs when actin filaments slide past myosin filaments towards the centre of the sarcomere due to the cyclic interactions of myosin crossbridges on the actin filaments.  These filaments are arranged on regular lattices in the sarcomere.  The M-band (M-line) maintains the myosin filaments in a hexagonal lattice and the Z-band (Z-line, Z-disc) maintains the actin filaments in a tetragonal lattice.  We study the 3D structure of these components in order to understand their role in the contraction of muscle.   The main techniques that we use are electron microscopy and electron tomography.

The current major project in our lab is understanding the 3D structure and organisation of myosin binding protein C (MyBP-C, also known as C-protein).  This is a 140 kD protein that binds to the thick filaments along bands of spacing 43 nm in the C-zones in each half of the A-band (see above figure and the electron micrograph).  The role of the protein is not fully understood but it is believed to be involved in regulation of contraction. There is much interest in this protein as mutations in the gene are a major cause of inherited heart disease, hypertrophic cardiomyopathy in which heart walls become greatly enlarged.  Understanding the role of this protein is imperative as it is estimated that more than 60 million people worldwide suffer from this condition. 

The beautiful animation below shows a cardiomyocyte (heart cell) in 3D.  This confocal microscope 3D image was produced by Professor Nick Severs. Anti-alpha actinin tagged with a fluorescent dye was used to label the Z-discs and light up the sarcomeres.  The cell is nearly cylindrical but has several jagged ends.  These are the sites of the intercalated discs and myocytes are "welded" to each other through the intercalated discs.  The jagged ends of the myocytes allow binding to more than one myocyte, hence cardiac muscle fibres have branched structures.