#sarcomeres

Dis-banded

Just like us, fruit flies are stripy beneath the skin. These sarcomeres – repeating bands of stretchy muscle tissue – contain fibres of myosin (highlighted in green) and actin (purple) griping and pulling at each other – as the sarcomeres shorten, the muscle contracts. This is heart muscle from fruit flies (Drosophila), used to investigate common faults in human heart disease. Compared to healthy muscle at the top, the sarcomeres at the bottom are much looser and swollen – in these hearts, researchers used RNA interference to hamper the activity of a protein called filamin, often shown to be altered in heart diseases like hypertrophic cardiomyopathy. Yet altering its activity in a different way – using CRISPR gene editing to change its structure – did not affect the flies as expected. Further studies might aim to solve this mystery, while altering genes and proteins reveals more about what we do, or perhaps don’t, have in common with Drosophila.

Written by John Ankers

Image from work by Flavie Ader and colleagues

Université Paris Cité, Paris, France

Image originally published with a Creative Commons Attribution – NonCommercial – NoDerivs (CC BY-NC-ND 4.0)

Published in Biology Open, September 2022

Architects Design Twisting Tower Inspired by Muscle Fibers for NYC Skyline

Turkish architecture firm Hayri Atak Architectural Design Studio has recently released images of Sarcostyle Tower— a 210-meter (689-foot) conceptual skyscraper that hopes to be an interesting addition to the New York City skyline. The futuristic renderings of this playful tower take great inspiration from biology. The project itself gets its name from the term sarcomeres, which is a complicated unit of striated muscle tissue. The organically connected bridges across the tower’s central void are designed to mimic the rod-shaped muscle fibers frozen in time. The architect behind Sarcostyle Tower further highlights this design move by creating a central void supported by a structural tube on each corner. As a result, the focus is pulled to the dynamic forms in the center of the building.

Disc Error

Studying life is often a matter of peeling back layers, revealing its workings piece by piece like a watchmaker with a pair of pliers. And when human tissues reveal something surprising, researchers often turn to simpler, similar organisms like fruit flies to fill in the gaps. Following their discovery of 'branches' between human sarcomeres – the short stretchy units that make up muscle fibres – a team of muscle biologists turns to the fly for answers. Yet they find altering the proteins involved also creates defects elsewhere in the muscle. Here they use 3D electron microscopy and artificial colours to highlight 'holes' in parts of the fly’s fibres called z-discs that the sarcomeres usually pull against to create tension. Revealing the delicate balances at play in muscle biology, the scientists are now looking for new ways to explore the role of branching in generating muscular forces.

Written by John Ankers

Video from work by Peter T. Ajayi and Prasanna Katti, and colleagues

Muscle Energetics Laboratory, NHLBI, NIH, Bethesda, MD, USA

Video originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in Nature Communications, May 2022

Shooting Messengers

In a hurry for a train, stretchy regions in our leg muscles called sarcomeres contract and expand to pull our bones along. Zooming in further on this mouse muscle, scientists follow molecules on their own journey – messenger RNAs (highlighted in red) are carrying genetic information, used as templates to build proteins. A technique called RNA FISH, spots RNAs travelling from the muscle fibre’s nuclei (where they’re made) to z-disks (blue) at the boundaries between sarcomeres along a muscle myofibre. The RNAs zip along the muscle’s network of microtubules (green) like tube or metro lines (although a billion times smaller). Scientists see patterns of different RNAs at the z-disks, clustering like cosmopolitan crowds of commuters at train stations – perhaps as a way to spread a variety of useful proteins along our muscles, which may be disrupted in myopathies.

Written by John Ankers

Image from work by Lance T. Denes, Chase P. Kelley & Eric T. Wang

Department of Molecular Genetics & Microbiology, Center for NeuroGenetics, Genetics Institute, University of Florida, Gainesville, FL, USA

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in Nature Communications, October 2021

Pull Yourself Together

If we could zoom in on our tensing muscles, we’d see bundles of thick and thin filaments pulling together. Speedy chemical reactions form tiny ‘cross bridges’ between them and, a bit like a climbers finding a grip, one filament pulls itself along the other. This happens all the way down a muscle fibre – repeating regions or sarcomeres shorten and the overall muscle contracts, helping us lift the heavy shopping, or climb a wall. Here researchers use electron cryotomography to blast mouse muscle with beams of electrons, mapping out contours from tiny deflections made in each electron’s path. A computer simulation lifts the image into 3D, highlighting separate filaments in rainbows colours. At this level of detail, researchers can zoom in on the molecular makeup of sarcomeres and their cross bridges (seen here as sticky-out branches on the filaments), giving insight into muscle biology and eventually injury and disease.

Written by John Ankers

Video from work by Zhexin Wang and Michael Grange, and colleagues

Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany

Video originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in Cell, March 2021

Hippo with Wings

Muscles are incredibly complex structures made up of long fibres, each up to several centimetres in length and packed with tiny strings known as myofibrils, which contract to generate muscular force. Building such complicated structures as an embryo grows into an animal is no easy task, so researchers are studying fruit fly wing muscles to figure out exactly which genes are involved and how they all work together. Some of the most important players are a group of genes that collectively form what’s known as the Hippo pathway: a series of interacting processes that control cell growth in many animals, including humans. These microscope images show muscles from fruit flies with various alterations in a key gene in the Hippo pathway known as Yorkie. Understanding how Yorkie and its partners work in muscle growth in flies helps to shed light on what’s going on during human muscle development and disease.

Written Kat Arney

Image adapted from work by Aynur Kaya-Çopur and colleagues

Aix Marseille University, CNRS, IBDM, Turing Center for Living Systems, Marseille, France

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in eLife, January 2021

Top: Cardiac muscle cells (Credit: Chrisopher Solis) Bottom: Chrisopher Solis (Credit: Kyle Dittloff)

NIH funds heart muscle cell research

Christopher Solis, a postdoctoral researcher in the UIC College of Medicine, has received a prestigious grant from the National Institutes of Health to fund his research into heart muscle cells and support his transition to an independent researcher. 

The grant, called a K99 Pathway to Independence Award, provides $200,000 over two years to fund his postdoctoral research, and then another $750,000 for three years after he secures a faculty position. Solis, who works in the lab of Brenda Russel, professor emerita of physiology and biophysics at UIC, is interested in how muscle cells in the heart respond to tension and more importantly, a reduction in tension. Heart cells are continually contracting and relaxing as they work to squeeze blood to the body. And like skeletal muscle cells, these cells can respond to increases in tension, or exertion, by growing in size. How cells react to a reduction in tension, known as ‘mechanical unloading’ in scientific circles, is the subject of Solis’s research project, which looks at structural changes in heart cells in the lab that have been dosed with a drug that reduces the strength of their contractions. 

“I am looking at how mechanical unloading affects the disassembly of protein-based structural elements in heart muscle cells called sarcomeres,” said Solis. “My hypothesis is that the degree of physical loading or unloading causes these elements to assemble and disassemble through the chemical tagging of these proteins, a process known as post-translational modification. I’ll be looking at signature of these protein tags in the cardiac sarcomeres to get a better idea of how this process works.”