Heidelberg scientists develop new methods to measure intracellular protein movement
Numerous obstacles posed by cellular structures hinder protein movements within the cell. Researchers from Heidelberg University and the German Cancer Research Center have succeeded in mapping the intracellular topology by observing proteins in living cells on multiple time and length scales.
By developing a new fluorescence microscopy-based technique, the researchers were able to measure how long it takes proteins to move over distances ranging from 0.2 to 3 micrometres in living cells. Under the direction of Dr. Karsten Rippe, the team analysed the data and developed a mathematical model to reconstruct the intracellular structures. The results of their research were published in “Nature Communications”.
Cellular structures such as membranes, the cytoskeleton and the DNA genome form a dynamic three-dimensional maze inside the cell. Proteins have to find their way through it to reach the sites where they are active. Accordingly, the spatial structure of the cell’s interior is a key factor for protein transport and cell function. “Cellular structures have been visualized in many microscopic studies.
But it is still unclear how the diffusing protein in the cell ‘senses’ this internal network of obstacles,” says Dr. Rippe. To address this question, his team devised a method to infer the cellular topology from the random motion of proteins. The team built their own fluorescence spectroscopy system to observe fluorescent proteins. According to Karsten Rippe, the largest obstacles were densely packed areas of DNA in the cell nucleus.
“A protein in a cell moves much like a marble in a labyrinth game, jockeying its way through the maze,” said Michael Baum, the study’s first author, who pursued the research as part of his PhD thesis at Heidelberg University. The marbles move easily over short distances, but then they encounter an obstacle and are slowed down as they move along.
This results in “stop-and-go” travelling with reduced average speed over longer distances. In their analysis of protein movements, the Heidelberg researchers mapped distances and corresponding translocation times needed for this travel, resulting in the average distance between obstacles. A mathematical model based on this data allowed the scientists to describe the measured movement of the proteins in the cell and reconstruct its topology – at a significantly better resolution than currently possible with light microscopy images, as Dr. Rippe points out.
“The obstacle structure encountered by a protein moving through the cell is porous, much like a sponge,” explains the Heidelberg researcher. Larger proteins were occasionally trapped in this dynamic structure for several minutes. Furthermore, drugs used in chemotherapy or to treat malaria were found to affect the mobility of proteins in the nucleus and make the DNA thicket more permeable. Dr. Rippe and his team now plan to apply their new approach in further experiments at the BioQuant Centre of Heidelberg University and the German Cancer Research Center. They will focus on the interrelation between drug-induced changes in the cell structure and protein transport as well as the disease-related deregulation of this process.
Funding for the research was provided by the Federal Ministry of Education and Research.
M. Baum, F. Erdel, M. Wachsmuth & K. Rippe: Retrieving the intracellular topology from multi-scale protein mobility mapping in living cells. Nature Communications 5, 4494 (24 July 2014), doi: 10.1038/ncomms5494
Dr. Karsten Rippe
Phone: +49 6221 54-51376
Communications and Marketing
Phone: +49 6221 542311
Marietta Fuhrmann-Koch | idw - Informationsdienst Wissenschaft
New photocatalyst speeds up the conversion of carbon dioxide into chemical resources
29.05.2017 | DGIST (Daegu Gyeongbuk Institute of Science and Technology)
Copper hydroxide nanoparticles provide protection against toxic oxygen radicals in cigarette smoke
29.05.2017 | Johannes Gutenberg-Universität Mainz
The world's highest gain high power laser amplifier - by many orders of magnitude - has been developed in research led at the University of Strathclyde.
The researchers demonstrated the feasibility of using plasma to amplify short laser pulses of picojoule-level energy up to 100 millijoules, which is a 'gain'...
Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.
Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....
Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.
The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....
An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
24.05.2017 | Event News
23.05.2017 | Event News
22.05.2017 | Event News
29.05.2017 | Earth Sciences
29.05.2017 | Life Sciences
29.05.2017 | Physics and Astronomy