Chemists reveal the force within you: New method for visualizing mechanical forces on cell surface

ScienceDaily (Nov. 9, 2011) — A new method for visualizing mechanical forces on the surface of a cell, reported in Nature Methods, provides the first detailed view of those forces, as they occur in real-time.

"Now we're able to measure something that's never been measured before: The force that one molecule applies to another molecule across the entire surface of a living cell, and as this cell moves and goes about its normal processes," says Khalid Salaita, assistant professor of biomolecular chemistry at Emory University. "And we can visualize these forces in a time-lapsed movie."

Salaita developed the florescent-sensor technique with chemistry graduate students Daniel Stabley and Carol Jurchenko, and undergraduate senior Stephen Marshall.

"Cells are constantly tugging and pushing on their surroundings, and they can even communicate with one another using mechanics," Salaita says. "One way that cells use forces is evident from the characteristic architecture of tissue, like a lung or a heart. If we want to really understand cells and how they work, we have to understand cell mechanics at a molecular level. The first step is to measure the tension applied to specific receptors on the cell surface."

The researchers demonstrated their technique on the epidermal growth factor receptor (EGFR), one of the most studied cellular signaling pathways. They mapped the mechanical strain exerted by EGFR during the early stages of endocytosis, when the protein receptor of a cell takes in a ligand, or binding molecule. The results showed that the cell does not passively absorb the ligand, but physically pulls it inside during the process. Their experiments provide the first direct evidence that force is exerted during endocytosis.

Mapping such forces may help to diagnose and treat diseases related to cellular mechanics. Cancer cells, for instance, move differently from normal cells, and it is unclear whether that difference is a cause or an effect of the disease.

"It's known that if EGFR is over-active, that can lead to cancer," Salaita says. "And one of the ways that EGFR is activated is by binding its ligand and taking it in. So if we can understand how tugging on EGFR force changes the pathway, and whether it plays a role in cancer, it might be possible to design drugs that target this pulling process."

Several methods have been developed in recent years to try to study the mechanics of cellular forces, but they have major limitations.

One genetic engineering approach requires splitting open and modifying proteins of a cell. This invasive technique may change the behavior of the cell, skewing the results.

The technique developed at Emory is non-invasive, does not modify the cell, and can be done with a standard fluorescence microscope. A flexible polymer is chemically modified at both ends. One end gets a fluorescence-based turn-on sensor that will bind to a receptor on the cell surface. The other end is chemically anchored to a microscope slide and a molecule that quenches fluorescence.

"Once a force is applied to the polymer, it stretches out," Salaita explains. "And as it extends, the distance from the quencher increases and the fluorescent signal turns on and grows brighter. We can determine the force being exerted by measuring the amount of fluorescent light emitted."

The forces of any individual protein or molecule on the cell surface can be measured using the technique, at far higher spatial and temporal resolutions than was previously possible.

Many mysteries beyond the biology and chemistry of cells may be explained through measuring cellular forces. How does a cancer cell crawl when a tumor spreads? What are the forces involved in cell division and immune response? What are the mechanics that allow groups of cardiac cells to beat in unison?

"Our method can be applied to nearly any receptor, opening the door to rapidly studying chemical and mechanical interactions across the thousands of membrane-bound receptors on the surface of virtually any cell type," Salaita says. "We hope that measuring cellular forces could then become part of the standard repertoire of biochemical techniques that scientists use to study living systems."

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Story Source:

The above story is reprinted from materials provided by Emory University. The original article was written by Carol Clark.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

Daniel R Stabley, Carol Jurchenko, Stephen S Marshall, Khalid S Salaita. Visualizing mechanical tension across membrane receptors with a fluorescent sensor. Nature Methods, 2011; DOI: 10.1038/nmeth.1747

Note: If no author is given, the source is cited instead.

Disclaimer: Views expressed in this article do not necessarily reflect those of ScienceDaily or its staff.

View the original article here

Chemists reveal the force within you: New method for visualizing mechanical forces on cell surface

ScienceDaily (Nov. 9, 2011) — A new method for visualizing mechanical forces on the surface of a cell, reported in Nature Methods, provides the first detailed view of those forces, as they occur in real-time.

"Now we're able to measure something that's never been measured before: The force that one molecule applies to another molecule across the entire surface of a living cell, and as this cell moves and goes about its normal processes," says Khalid Salaita, assistant professor of biomolecular chemistry at Emory University. "And we can visualize these forces in a time-lapsed movie."

Salaita developed the florescent-sensor technique with chemistry graduate students Daniel Stabley and Carol Jurchenko, and undergraduate senior Stephen Marshall.

"Cells are constantly tugging and pushing on their surroundings, and they can even communicate with one another using mechanics," Salaita says. "One way that cells use forces is evident from the characteristic architecture of tissue, like a lung or a heart. If we want to really understand cells and how they work, we have to understand cell mechanics at a molecular level. The first step is to measure the tension applied to specific receptors on the cell surface."

The researchers demonstrated their technique on the epidermal growth factor receptor (EGFR), one of the most studied cellular signaling pathways. They mapped the mechanical strain exerted by EGFR during the early stages of endocytosis, when the protein receptor of a cell takes in a ligand, or binding molecule. The results showed that the cell does not passively absorb the ligand, but physically pulls it inside during the process. Their experiments provide the first direct evidence that force is exerted during endocytosis.

Mapping such forces may help to diagnose and treat diseases related to cellular mechanics. Cancer cells, for instance, move differently from normal cells, and it is unclear whether that difference is a cause or an effect of the disease.

"It's known that if EGFR is over-active, that can lead to cancer," Salaita says. "And one of the ways that EGFR is activated is by binding its ligand and taking it in. So if we can understand how tugging on EGFR force changes the pathway, and whether it plays a role in cancer, it might be possible to design drugs that target this pulling process."

Several methods have been developed in recent years to try to study the mechanics of cellular forces, but they have major limitations.

One genetic engineering approach requires splitting open and modifying proteins of a cell. This invasive technique may change the behavior of the cell, skewing the results.

The technique developed at Emory is non-invasive, does not modify the cell, and can be done with a standard fluorescence microscope. A flexible polymer is chemically modified at both ends. One end gets a fluorescence-based turn-on sensor that will bind to a receptor on the cell surface. The other end is chemically anchored to a microscope slide and a molecule that quenches fluorescence.

"Once a force is applied to the polymer, it stretches out," Salaita explains. "And as it extends, the distance from the quencher increases and the fluorescent signal turns on and grows brighter. We can determine the force being exerted by measuring the amount of fluorescent light emitted."

The forces of any individual protein or molecule on the cell surface can be measured using the technique, at far higher spatial and temporal resolutions than was previously possible.

Many mysteries beyond the biology and chemistry of cells may be explained through measuring cellular forces. How does a cancer cell crawl when a tumor spreads? What are the forces involved in cell division and immune response? What are the mechanics that allow groups of cardiac cells to beat in unison?

"Our method can be applied to nearly any receptor, opening the door to rapidly studying chemical and mechanical interactions across the thousands of membrane-bound receptors on the surface of virtually any cell type," Salaita says. "We hope that measuring cellular forces could then become part of the standard repertoire of biochemical techniques that scientists use to study living systems."

Recommend this story on Facebook, Twitter,
and Google +1:

Other bookmarking and sharing tools:

Story Source:

The above story is reprinted from materials provided by Emory University. The original article was written by Carol Clark.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

Daniel R Stabley, Carol Jurchenko, Stephen S Marshall, Khalid S Salaita. Visualizing mechanical tension across membrane receptors with a fluorescent sensor. Nature Methods, 2011; DOI: 10.1038/nmeth.1747

Note: If no author is given, the source is cited instead.

Disclaimer: Views expressed in this article do not necessarily reflect those of ScienceDaily or its staff.

View the original article here

Exotic behavior when mechanical devices reach the nanoscale

ScienceDaily (May 15, 2011) — Mechanical resonators are extensively used in high-tech industry, to mark time in electronic components, and to stabilize radio transmissions. Most mechanical resonators damp (slow down) in a well-understood linear manner, but ground-breaking work by Prof. Adrian Bachtold and his research group at the Catalan Institute of Nanotechnology has shown that resonators formed from nanoscale graphene and carbon nanotubes exhibit nonlinear damping, opening up exciting possibilities for super-sensitive detectors of force or mass.

In an article recently published in Nature Nanotechnology Prof. Bachtold and his co-researchers describe how they formed nano-scale resonators by suspending tiny graphene sheets or carbon nanotubes and clamping them at each end. These devices, similar to guitar strings, can be set to vibrate at very specific frequencies.

In all mechanical resonators studied to date, from large objects several metres in size down to tiny components just a few tens of nanometers in length, damping has always been observed to occur in a highly predictable, linear manner. However Prof. Bachtold´s research demonstrates that this linear damping paradigm breaks down for resonators with critical dimensions on the atomic scale. Of particular importance they have shown that the damping is strongly nonlinear for resonators based on nanotubes and graphene, a characteristic that facilitates amplification of signals and dramatic improvements in sensitivity.

The finding has profound consequences. Damping is central to the physics of nanoelectromechanical resonators, lying at the core of quantum and sensing experiments. Therefore many predictions that have been made for nanoscale electro-mechanical devices now need to be revisited when considering nanotube and graphene resonators.

This new insight into the dynamics of nano-scale resonators will also enable dramatic improvements in the performance of numerous devices. Already the Prof. Bachtold´s group has achieved a new record in quality factor for graphene resonators and ultra-weak force sensing with a nanotube resonator.

The work is particularly timely because an increasing number of research groups around the world with diverse backgrounds are choosing to study nanotube/graphene resonators, which have a number of uniquely useful properties.

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Institut Català de Nanotecnologia, via EurekAlert!, a service of AAAS.

Journal Reference:

A. Eichler, J. Moser, J. Chaste, M. Zdrojek, I. Wilson-Rae, A. Bachtold. Nonlinear damping in mechanical resonators made from carbon nanotubes and graphene. Nature Nanotechnology, 2011; DOI: 10.1038/NNANO.2011.71

Note: If no author is given, the source is cited instead.

Disclaimer: Views expressed in this article do not necessarily reflect those of ScienceDaily or its staff.

View the original article here

Exotic behavior when mechanical devices reach the nanoscale

ScienceDaily (May 15, 2011) — Mechanical resonators are extensively used in high-tech industry, to mark time in electronic components, and to stabilize radio transmissions. Most mechanical resonators damp (slow down) in a well-understood linear manner, but ground-breaking work by Prof. Adrian Bachtold and his research group at the Catalan Institute of Nanotechnology has shown that resonators formed from nanoscale graphene and carbon nanotubes exhibit nonlinear damping, opening up exciting possibilities for super-sensitive detectors of force or mass.

In an article recently published in Nature Nanotechnology Prof. Bachtold and his co-researchers describe how they formed nano-scale resonators by suspending tiny graphene sheets or carbon nanotubes and clamping them at each end. These devices, similar to guitar strings, can be set to vibrate at very specific frequencies.

In all mechanical resonators studied to date, from large objects several metres in size down to tiny components just a few tens of nanometers in length, damping has always been observed to occur in a highly predictable, linear manner. However Prof. Bachtold´s research demonstrates that this linear damping paradigm breaks down for resonators with critical dimensions on the atomic scale. Of particular importance they have shown that the damping is strongly nonlinear for resonators based on nanotubes and graphene, a characteristic that facilitates amplification of signals and dramatic improvements in sensitivity.

The finding has profound consequences. Damping is central to the physics of nanoelectromechanical resonators, lying at the core of quantum and sensing experiments. Therefore many predictions that have been made for nanoscale electro-mechanical devices now need to be revisited when considering nanotube and graphene resonators.

This new insight into the dynamics of nano-scale resonators will also enable dramatic improvements in the performance of numerous devices. Already the Prof. Bachtold´s group has achieved a new record in quality factor for graphene resonators and ultra-weak force sensing with a nanotube resonator.

The work is particularly timely because an increasing number of research groups around the world with diverse backgrounds are choosing to study nanotube/graphene resonators, which have a number of uniquely useful properties.

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Institut Català de Nanotecnologia, via EurekAlert!, a service of AAAS.

Journal Reference:

A. Eichler, J. Moser, J. Chaste, M. Zdrojek, I. Wilson-Rae, A. Bachtold. Nonlinear damping in mechanical resonators made from carbon nanotubes and graphene. Nature Nanotechnology, 2011; DOI: 10.1038/NNANO.2011.71

Note: If no author is given, the source is cited instead.

Disclaimer: Views expressed in this article do not necessarily reflect those of ScienceDaily or its staff.

View the original article here