University of Freiburg researchers have applied super-resolution methods to study the organization of receptors on B lymphocytesAntigen receptors on B lymphocytes sense foreign molecules, such as pathogens or vaccines, and activate the B cells to produce antibodies that protect humans against many diseases. Prof. Dr. Michael Reth, Scientific Director of BIOSS Centre for Biological Signalling Studies, and his group have applied three different super-resolution methods to study the distribution of the two major classes of antigen receptors on mature B lymphocytes: Immunoglobulin M (IgM) and Immunoglobulin D (IgD). 
Researchers previously assumed that receptors such as the antigen receptors of class Immunoglobulin M (IgM) and Immunoglobulin D (IgD) are freely diffusing and equally distributed molecules on the membrane (image above). However, the new study shows that these antigen receptors are organized in different membrane compartments, also called "protein islands", with diameters of 150-200 nanometers (image below). This finding is another indication that, at nanoscale distance, the proteins on cellular membranes are highly organized. (Image: Research Group Reth) It had been previously assumed that all proteins on the membrane, including receptors, are freely diffusing molecules that only become organized upon binding to specific ligands. Reth’s group found out that IgM and IgD receptors are organized in protein islands. The researchers from the University of Freiburg collaborated with Prof. Dr. Hassan Jumaa from the University of Ulm/Germany and Prof. Dr. Björn F. Lillemeier from the Salk Institute in La Jolla/USA. The imaging analysis was conducted in collaboration with Dr. Olaf Ronneberger’s group, computer scientist at the University of Freiburg. The team has published their research findings in the journal ("B cell antigen receptors of the IgM and IgD classes are clustered in different protein islands that are altered during B cell activation"). The researchers hope that these new insights into the nanoscale organization of antigen receptors will support the design of more efficient vaccines or better treatments for B cell tumors where membrane organization is often altered. Using two-color direct stochastical optical reconstruction microscopy (dSTORM), the researchers found that IgM and IgD reside on the plasma membrane of resting B cells in separated protein islands of approximately 150 and 240 nanometers (nm), respectively. This class-specific compartmentalization of the antigen receptors is also detected by transmission electron microscopy (TEM) and Fab-based proximity-ligation assay (Fab-PLA) studies. Upon B cell activation, the IgM and IgD protein islands became smaller and the two classes of receptors are now found in close proximity to each other. These studies provide direct evidence for the nanoscale compartmentalization of the lymphocyte membrane. Furthermore, they suggest that upon B cell activation, the different IgM and IgD protein islands form nano-synapses which allow the exchange of lipids and proteins. This could explain how the IgM class antigen receptors find contact to Raft-associated lipids and proteins. The association of IgM with these lipids is a well-known hallmark of B cell activation. Michael Reth is professor of molecular immunology at the Institute of Biology III at the University of Freiburg and speaker of the Cluster of Excellence BIOSS Centre for Biological Signalling Studies. Palash Maity, lead author of the study, is a postdoc at BIOSS and at the Max Planck Institute of Immunobiology and Epigenetics in Freiburg. Olaf Ronneberger is working at the Institute of Computer Science. Ronneberger and Hassan Jumaa are both members of BIOSS Centre for Biological Signalling Studies. This study is part of the BIOSS nanoscale explorer program (BiNEP), which is a focus topic in the BIOSS-2 research program. In this program, BIOSS is developing methods to better understand the nanoworld of signaling processes, beyond the 250 nm diffraction limit of visible light.
read more "A glimpse into the nanoworld of lymphocyte cell membranes"
Researchers previously assumed that receptors such as the antigen receptors of class Immunoglobulin M (IgM) and Immunoglobulin D (IgD) are freely diffusing and equally distributed molecules on the membrane (image above). However, the new study shows that these antigen receptors are organized in different membrane compartments, also called "protein islands", with diameters of 150-200 nanometers (image below). This finding is another indication that, at nanoscale distance, the proteins on cellular membranes are highly organized. (Image: Research Group Reth) It had been previously assumed that all proteins on the membrane, including receptors, are freely diffusing molecules that only become organized upon binding to specific ligands. Reth’s group found out that IgM and IgD receptors are organized in protein islands. The researchers from the University of Freiburg collaborated with Prof. Dr. Hassan Jumaa from the University of Ulm/Germany and Prof. Dr. Björn F. Lillemeier from the Salk Institute in La Jolla/USA. The imaging analysis was conducted in collaboration with Dr. Olaf Ronneberger’s group, computer scientist at the University of Freiburg. The team has published their research findings in the journal ("B cell antigen receptors of the IgM and IgD classes are clustered in different protein islands that are altered during B cell activation"). The researchers hope that these new insights into the nanoscale organization of antigen receptors will support the design of more efficient vaccines or better treatments for B cell tumors where membrane organization is often altered. Using two-color direct stochastical optical reconstruction microscopy (dSTORM), the researchers found that IgM and IgD reside on the plasma membrane of resting B cells in separated protein islands of approximately 150 and 240 nanometers (nm), respectively. This class-specific compartmentalization of the antigen receptors is also detected by transmission electron microscopy (TEM) and Fab-based proximity-ligation assay (Fab-PLA) studies. Upon B cell activation, the IgM and IgD protein islands became smaller and the two classes of receptors are now found in close proximity to each other. These studies provide direct evidence for the nanoscale compartmentalization of the lymphocyte membrane. Furthermore, they suggest that upon B cell activation, the different IgM and IgD protein islands form nano-synapses which allow the exchange of lipids and proteins. This could explain how the IgM class antigen receptors find contact to Raft-associated lipids and proteins. The association of IgM with these lipids is a well-known hallmark of B cell activation. Michael Reth is professor of molecular immunology at the Institute of Biology III at the University of Freiburg and speaker of the Cluster of Excellence BIOSS Centre for Biological Signalling Studies. Palash Maity, lead author of the study, is a postdoc at BIOSS and at the Max Planck Institute of Immunobiology and Epigenetics in Freiburg. Olaf Ronneberger is working at the Institute of Computer Science. Ronneberger and Hassan Jumaa are both members of BIOSS Centre for Biological Signalling Studies. This study is part of the BIOSS nanoscale explorer program (BiNEP), which is a focus topic in the BIOSS-2 research program. In this program, BIOSS is developing methods to better understand the nanoworld of signaling processes, beyond the 250 nm diffraction limit of visible light.
Artist’s rendering of a new carbon-based catalyst that can bond to the edges of two-dimensional sheets of graphene. (Illustration: Jose-Luis Olivares/MIT) Catalysts enhance the rate of a chemical reaction but are not consumed in the process. As a result, the repeated action of very small amounts of a catalyst can have large and long-lasting effects. There are two basic types of electrocatalysts, which are crucial for enabling reactions in devices such as fuel cells or electrolyzers. Molecular electrocatalysts have the advantage of being relatively easy to tune by chemical treatment, so their reactivity and selectivity match the desired application; heterogeneous electrocatalysts, which are much more durable and easy to process into a device, tend to lack that ability for precise control. “What we wanted to do was to figure out a way to bridge those two worlds,” Surendranath explains. His team was able to accomplish that by taking graphite and finding a way to chemically modify its surface to give it the desired tunability. The basic material used is pure carbon, which is “the universal electrode material” in batteries and fuel cells, Surendranath says. By finding a way to make this material tunable in the same ways as molecular catalysts, the researchers are providing an opening to a new approach to the design of such materials, which are also a key part of many chemical manufacturing processes. In addition to their possible uses in fuel cells, such new catalysts could also be useful for enhancing chemical reactions, such as reducing carbon dioxide to convert it into a usable fuel, Surendranath says. This could reduce emissions of a principal greenhouse gas that fosters climate change, and transform it into a useful, renewable fuel. The initial finding described in this paper is “just one piece of what we believe is a large iceberg,” Surendranath adds, since the basic ingredient is “a dirt cheap material that we are modifying using well-known chemistry.” One frequent barrier to taking systems that work in the laboratory and making them into practical, marketable products is the ability to scale up the production process. “You need to be able to scale efficiently,” Surendranath says. The fact that the basis for the new catalyst is “a class of materials that are already made at scale, for commodities like paint and rubber,” should make scaling up their process relatively straightforward, he says: “All the keys to that are already in place.” Surendranath says that this finding is particularly exciting because chemists “usually take a very precise refined material and then engineer some of its properties. But in this case, it allows us to take a material that is cheap and abundant, and turn it into something very valuable. It’s a different paradigm.”