Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Force, not light, gives MIT researchers images of cell receptors

13.06.2007
--Technique could assist in the design and testing of new drug molecules

MIT researchers have found a way to glimpse interactions between molecules on the surface of a cell.

By measuring the force generated by these cell surface interactions, the MIT team was able to image and measure the rate at which individual molecules join and separate from receptors on the cell surface. These interactions are not visible with traditional light microscopy.

"We were able to measure regions of strong intermolecular binding on the cell surfaces, which enabled us to map the locations of the receptors," said Sunyoung Lee, a graduate student in the Department of Materials Science and Engineering and lead author of a paper on the work in the June 5 issue of the Proceedings of the National Academy of Sciences.

... more about:
»Vliet »cytoskeleton »interactions »kinetics »receptor

The technique, known as functionalized force imaging, could allow researchers to better understand the strength and rates of interactions between molecular ligands outside the cell and the molecular receptors on the cell surface. These interactions play a critical role in cell growth, proliferation and differentiation. It could also assist in the design and testing of new drug molecules that bind strongly or quickly to the target cell.

Receptors on the cell surface allow the cell to maintain constant communication with its environment-they bind to molecules that convey information about the environment and instructions telling them what functions to carry out. In this study, the researchers looked at a receptor called vascular endothelial growth factor receptor-2 (VEGFR2), which is important for the proliferation, migration and differentiation of the vascular endothelial cells that line blood vessels.

Researchers in the lab of Krystyn Van Vliet, senior author of the PNAS study, are working to understand the kinetics of cell-molecule interactions and how a cell responds to mechanical and chemical changes in its environment. These changes in function can be evidenced by the number and type of receptors displayed on their surfaces.

"You can ask specific questions about how the mechanical and chemical stimuli outside the cell generate changes in cell surfaces and structures within the cell," said Van Vliet, the Thomas Lord Assistant Professor of Materials Science and Engineering.

With traditional light-based (optical) microscopy, you can see large cell structures like the nucleus and cytoskeleton, but not tiny molecules such as individual receptors on the living cell surface. To achieve the nanometer-scale spatial resolution required to see these molecules on the cell surface, the researchers used mechanical force, rather than light.

To pull a bound molecule from its target receptor, a very small force of about 100 piconewtons is required. The researchers measured that force by attaching anti-VEGFR2 antibody molecules to the end of a cantilevered probe in a scanning probe microscope. The cantilever oscillates in a regular pattern as it scans along the cell surface, and whenever the pattern is disturbed, the researchers can infer that the antibody on the probe has bound or "stuck" to its target receptor, VEGFR2.

By mapping those reversible interactions at every point on the cell surface, the researchers can determine where the receptors are located with respect to other cell structures. More importantly, said Van Vliet, they can follow the molecular interactions on the cell over time, allowing them to determine the binding kinetics, or the rate at which molecules join and separate from the cell surface.

The force-based imaging also allows for visualization of the stiff cytoskeleton underneath the cell surface, which provides internal structure for the cell. By overlapping images of the cytoskeleton and the VEGF receptors, the researchers found that most of the receptors were located near the cytoskeleton. Such correlations support the current hypothesis that VEGF receptor function is linked to that of other cell surface proteins including integrins, which transmit mechanical forces from the outside to the inside of the cell, Van Vliet said.

Other researchers have used this approach to measure binding forces in isolated proteins, but the MIT team shows that these tiny forces can also be used to visualize binding kinetics on chemically fixed

(nonliving) cells and living cells.

"It's challenging to do this on cells because their surfaces are made up of many different kinds of molecules, which makes them topographically rough, chemically diverse, and mechanically compliant," said Van Vliet.

Van Vliet and Lee outlined several possible applications of functionalized force imaging on endothelial, cancer and stem cells, including identification of target receptors for cell-specific drugs; comparison of kinetics for individual and clustered receptors; and visualizing how the mechanical stiffness of extracellular materials alters cell function and cell surface receptor activity over time.

The research was funded by the National Science Foundation Nanoscale Exploratory Research, the Center for the Integration of Medicine and Innovative Technology, the Hugh Hampton Young Memorial Foundation and the Beckman Foundation Young Investigators Program.

Elizabeth A. Thomson | MIT News Office
Further information:
http://www.mit.edu

Further reports about: Vliet cytoskeleton interactions kinetics receptor

More articles from Life Sciences:

nachricht Bare bones: Making bones transparent
27.04.2017 | California Institute of Technology

nachricht Link Discovered between Immune System, Brain Structure and Memory
26.04.2017 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

Bare bones: Making bones transparent

27.04.2017 | Life Sciences

Study offers new theoretical approach to describing non-equilibrium phase transitions

27.04.2017 | Physics and Astronomy

From volcano's slope, NASA instrument looks sky high and to the future

27.04.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>