Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

First simulation of a full-sized mitochondrial membrane

08.05.2020

New algorithm links different scales, bringing simulated cell a step closer

Scientists from the University of Groningen have developed a method that combines different resolution levels in a computer simulation of biological membranes.


Snapshot of the membranes of an entire organelle, a mitochondrion, simulated for the first time at molecular resolution.

Credit: Marrink Lab, University of Groningen

Their algorithm backmaps a large-scale model that includes features, such as membrane curvature, to its corresponding coarse-grained molecular model. This has allowed them to zoom in on toxin-induced membrane budding and to simulate a full-sized mitochondrial lipid membrane.

Their approach, which was published in the journal Nature Communications on 8 May, opens the way to whole-cell simulations at a molecular level.

Molecular dynamics simulations are a powerful tool to study the movements and interactions of atoms and molecules. However, in many biological processes, large-scale changes in, for example, membrane shape are important. 'These shape changes are of fundamental importance to the cell's functioning,' explains Siewert-Jan Marrink, Professor of Molecular Dynamics at the University of Groningen.

'However, the time and length scale of these membrane shape changes are too large for simulations at a molecular resolution.'

Challenging

Even though an increase in computing power allows more complex and longer simulations, cell structures such as mitochondria are still beyond reach. That is why the Molecular Dynamics group has developed an algorithm that links large-scale changes to molecular level simulations.

For mitochondria, they started with an electron micrograph density map. The densities were translated into lipid structures and these were used as the input for a molecular dynamics simulation with the Coarse Grain (CG) Martini force field, previously developed by Marrink.

'The difficult part is to place the lipids in the correct orientation in this density map, which is especially challenging in bent areas,' adds Wria Pezeshkian, a postdoctoral researcher in Marrink's team and co-author of the paper. The algorithm allows users to add different kinds of lipids to the membrane, at a realistic packing level.

Using this approach, Marrink and his colleagues were able to simulate the entire lipid membrane of a mitochondrion for two nanoseconds. Pezeshkian: 'This structure contained more than five million lipids, which meant that the simulation had to deal with 80 million particles as each lipid molecule consists of multiple particles.'

Triangles

Considering the size and shape, this simulation's complexity is larger than any simulation performed previously. 'A simulation of microseconds would have been possible but, as we had no information on the localization of the proteins in the mitochondrial membrane, it only contained lipids and is therefore unstable,' explains Marrink. Adding this extra complexity to the simulation is certainly possible and is currently in progress.

Instead of a density map, the input for the system could also be a continuum model, which represents the membrane surface as triangles made up of nodes that are connected by 'springs'. Such a model can calculate forces generated by membrane deformation. Backmapping lipids and toxin proteins onto the corresponding parts of this model allowed Marrink and his colleagues to zoom in on molecular behaviour in the stalk of a membrane bud that was induced by the joint action of many toxins.

Synthetic cell

'Our final goal is to simulate an entire eukaryotic cell and zoom in on specific parts of this object,' says Marrink. This is currently out of reach, although the current system already allows simulation of large objects inside a cell, such as the endoplasmic reticulum or the Golgi apparatus. 'And we could probably simulate a red blood cell.'

A simple synthetic cell may soon be within reach. Marrink is involved in a project aimed at creating a synthetic cell and being able to simulate processes such as cell division would help its design. 'We would really like to know which lipids and proteins could play a role in cell constriction during division.'

###

Simple Science Summary

Scientists use computer simulations to study the interaction of molecules in cells. However, many interactions are affected by processes on a time and length scale that is beyond the current limits for molecular simulations. Scientists from the University of Groningen have therefore developed a system where they use input from either density maps or large-scale models and zoom in on selected parts. These are then studied using detailed simulations at a molecular level. Using this technique, they successfully simulated the entire membrane of a mitochondrion, a large organelle inside cells. This technique enables the simulation of a variety of cell organelles and is a stepping stone towards simulations of entire cells.

Reference: Weria Pezeshkian, Melanie König, Tsjerk A. Wassenaar and Siewert J. Marrink: Backmapping triangulated surfaces to coarse-grained membrane models. Nature Communications, 8 May 2020

Rene Fransen | EurekAlert!
Further information:
http://dx.doi.org/10.1038/s41467-020-16094-y

More articles from Life Sciences:

nachricht Rising water temperatures could endanger the mating of many fish species
03.07.2020 | Alfred-Wegener-Institut, Helmholtz-Zentrum für Polar- und Meeresforschung

nachricht Moss protein corrects genetic defects of other plants
03.07.2020 | Rheinische Friedrich-Wilhelms-Universität Bonn

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

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...

Im Focus: Gentle wall contact – the right scenario for a fusion power plant

Quasi-continuous power exhaust developed as a wall-friendly method on ASDEX Upgrade

A promising operating mode for the plasma of a future power plant has been developed at the ASDEX Upgrade fusion device at Max Planck Institute for Plasma...

Im Focus: ILA Goes Digital – Automation & Production Technology for Adaptable Aircraft Production

Live event – July 1, 2020 - 11:00 to 11:45 (CET)
"Automation in Aerospace Industry @ Fraunhofer IFAM"

The Fraunhofer Institute for Manufacturing Technology and Advanced Materials IFAM l Stade is presenting its forward-looking R&D portfolio for the first time at...

Im Focus: AI monitoring of laser welding processes - X-ray vision and eavesdropping ensure quality

With an X-ray experiment at the European Synchrotron ESRF in Grenoble (France), Empa researchers were able to demonstrate how well their real-time acoustic monitoring of laser weld seams works. With almost 90 percent reliability, they detected the formation of unwanted pores that impair the quality of weld seams. Thanks to a special evaluation method based on artificial intelligence (AI), the detection process is completed in just 70 milliseconds.

Laser welding is a process suitable for joining metals and thermoplastics. It has become particularly well established in highly automated production, for...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
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

Aachen Machine Tool Colloquium AWK'21 will take place on June 10 and 11, 2021

07.04.2020 | Event News

 
Latest News

Rising water temperatures could endanger the mating of many fish species

03.07.2020 | Life Sciences

Risk of infection with COVID-19 from singing: First results of aerosol study with the Bavarian Radio Chorus

03.07.2020 | Studies and Analyses

Efficient, Economical and Aesthetic: Researchers Build Electrodes from Leaves

03.07.2020 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>