Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Fantastic muscle proteins and where to find them

22.06.2020

Researchers at the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) developed a mouse model that enables them to look inside a working muscle and identify the proteins that allow the sarcomere to contract, relax, communicate its energy needs, and adapt to exercise. Specifically, they were able to map proteins in defined subregions of the sarcomere, starting from the "Z-disc," the boundary between neighboring sarcomeres. This in and of itself was a significant step forward in the study of striated muscle.

In the process, they made an unexpected discovery: myosin, one of the three main proteins that make up striated muscle fibers, appears to enter the Z-disc.


Watching the sarcomeres contract - collage of myosin (green), actin and the Z-disk (red) and BioID (blue).

Credit: Jacobo Lopez Carballo, Gotthardt Lab, MDC

Usage Restrictions: Only use in course of reporting on this study.

Models of how myosin, actin and the elastic scaffold protein titin work together have largely ignored the possibility that myosin filaments penetrate the Z-disc structure. Only recently have German scientists theorized that they do, but no experimental evidence has validated the model, until now.

"This is going to be unexpected even for myosin researchers," says Professor Michael Gotthardt, who heads MDC's Neuromuscular and Cardiovascular Cell Biology Lab and led the research. "It gets to the very basics of how muscles generate force."

Who's there?

Gotthardt's team including first authors Dr. Franziska Rudolph and Dr. Claudia Fink with the help from colleagues at the MDC and the University of Göttingen, never set out to validate this theory. Their primary goal was to identify the proteins in and near the Z-disc.

To do this, they developed a mouse model with an artificial enzyme, called BioID, inserted into the giant protein titin. The Titin-BioID then tagged proteins close to the Z-disc.

Sarcomeres are tiny molecular machines, packed with proteins that tightly interact. Until now it has been impossible to separate proteins specific to the different subregions, especially in live, functioning muscle. "Titin-BioID probes specific regions of the sarcomere structure in vivo," says Dr. Philipp Mertins, who heads MDC's Proteomics Lab. "This has not been possible before."

The team is the first to use BioID in live animals under physiological conditions and identified 450 proteins associated with the sarcomere, of which about half were already known. They found striking differences between heart and skeletal muscle, and adult versus neonatal mice, which relate to sarcomere structure, signaling and metabolism.

These differences reflect the need of adult tissue to optimize performance and energy production versus growth and remodeling in neonatal tissue.

"We wanted to know who's there, know who the players are," Gotthardt says. "Most were expected, validating our approach."

The surprise

The protein that they were not expecting to see in the Z-disc was myosin, which is integrated at the opposite site of the sarcomere. When a muscle is triggered to move, myosin walks along actin bringing neighboring Z-discs closer together. This sliding of actin and myosin filaments creates the force that enables our heart to pump blood or our skeletal muscle to maintain posture, or lift an object.

This so-called "sliding filament model" of the sarcomere describes force production and helps explain how force and sarcomere length relate. However, current models have trouble predicting the behavior of fully contracted sarcomeres. Those models have assumed myosin does not enter the Z-disc on its walk along actin. There have been some hints that maybe it keeps going.

"But we didn't know if what we were seeing in stained tissue samples was an artefact or real life," Gotthardt says. "With BioID we can sit at the Z-disc and watch myosin pass by."

Gotthardt agrees with the proposed theory that myosin entering the Z-disc can limit or dampen the contraction. This might help solve the ongoing issue scientists have had calculating how much force a muscle fiber can create in relation to its length and lead to a refined model of the sarcomere and possibly serve to protect muscle from excessive contraction.

Why it matters

Understanding how muscle fibers extend and contract on the molecular level under normal conditions is important so researchers can then identify what is going wrong when muscles are damaged, diseased or atrophy with age. Identifying which proteins are causing problems could potentially help identify novel treatment targets for patients with heart disease or skeletal muscle disorders.

Gotthardt and his team plan to next use BioID to study animals with different pathologies, to see what proteins are involved in muscle atrophy, for example. "Maybe a protein that is not normally there goes into the sarcomere, and it is part of the pathology," Gotthardt says. "We can find it with BioID."

###

The Max Delbrück Center for Molecular Medicine (MDC)

The Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) was founded in Berlin in 1992. It is named for the German-American physicist Max Delbrück, who was awarded the 1969 Nobel Prize in Physiology and Medicine. The MDC's mission is to study molecular mechanisms in order to understand the origins of disease and thus be able to diagnose, prevent and fight it better and more effectively. In these efforts the MDC cooperates with the Charité - Universitätsmedizin Berlin and the Berlin Institute of Health (BIH ) as well as with national partners such as the German Center for Cardiovascular Research and numerous international research institutions. More than 1,600 staff and guests from nearly 60 countries work at the MDC, just under 1,300 of them in scientific research. The MDC is funded by the German Federal Ministry of Education and Research (90 percent) and the State of Berlin (10 percent), and is a member of the Helmholtz Association of German Research Centers. http://www.mdc-berlin.de

Media Contact

Professor Michael Gotthardt
gotthardt@mdc-berlin.de
49-309-406-2245

http://www.mdc-berlin.de 

Professor Michael Gotthardt | EurekAlert!
Further information:
http://dx.doi.org/10.1038/s41467-020-16929-8

Further reports about: Cardiovascular MDC Z-disc muscle fibers myosin filaments proteins skeletal muscle

More articles from Life Sciences:

nachricht Polarization of Br2 molecule in vanadium oxide cluster cavity and new alkane bromination
13.07.2020 | Kanazawa University

nachricht Researchers present concept for a new technique to study superheavy elements
13.07.2020 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Electron cryo-microscopy: Using inexpensive technology to produce high-resolution images

Biochemists at Martin Luther University Halle-Wittenberg (MLU) have used a standard electron cryo-microscope to achieve surprisingly good images that are on par with those taken by far more sophisticated equipment. They have succeeded in determining the structure of ferritin almost at the atomic level. Their results were published in the journal "PLOS ONE".

Electron cryo-microscopy has become increasingly important in recent years, especially in shedding light on protein structures. The developers of the new...

Im Focus: The spin state story: Observation of the quantum spin liquid state in novel material

New insight into the spin behavior in an exotic state of matter puts us closer to next-generation spintronic devices

Aside from the deep understanding of the natural world that quantum physics theory offers, scientists worldwide are working tirelessly to bring forth a...

Im Focus: Excitation of robust materials

Kiel physics team observed extremely fast electronic changes in real time in a special material class

In physics, they are currently the subject of intensive research; in electronics, they could enable completely new functions. So-called topological materials...

Im Focus: Electrons in the fast lane

Solar cells based on perovskite compounds could soon make electricity generation from sunlight even more efficient and cheaper. The laboratory efficiency of these perovskite solar cells already exceeds that of the well-known silicon solar cells. An international team led by Stefan Weber from the Max Planck Institute for Polymer Research (MPI-P) in Mainz has found microscopic structures in perovskite crystals that can guide the charge transport in the solar cell. Clever alignment of these "electron highways" could make perovskite solar cells even more powerful.

Solar cells convert sunlight into electricity. During this process, the electrons of the material inside the cell absorb the energy of the light....

Im Focus: The lightest electromagnetic shielding material in the world

Empa researchers have succeeded in applying aerogels to microelectronics: Aerogels based on cellulose nanofibers can effectively shield electromagnetic radiation over a wide frequency range – and they are unrivalled in terms of weight.

Electric motors and electronic devices generate electromagnetic fields that sometimes have to be shielded in order not to affect neighboring electronic...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Contact Tracing Apps against COVID-19: German National Academy Leopoldina hosts international virtual panel discussion

07.07.2020 | Event News

International conference QuApps shows status quo of quantum technology

02.07.2020 | Event News

Dresden Nexus Conference 2020: Same Time, Virtual Format, Registration Opened

19.05.2020 | Event News

 
Latest News

Black phosphorus-based van der Waals heterostructures for mid-infrared light-emission applications

13.07.2020 | Physics and Astronomy

Polarization of Br2 molecule in vanadium oxide cluster cavity and new alkane bromination

13.07.2020 | Life Sciences

Researchers present concept for a new technique to study superheavy elements

13.07.2020 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>