Chemists reveal the force within you

By Carol Clark

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.

"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." Graphic by Daniel Stabley.

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 new technique for visualizing cellular forces uses a standard fluorescence microscope.

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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The spirit of Emory came from a lab

From Emory Magazine:

Does any other university have a biology lab skeleton as its mascot? We think it unlikely. As mascots go, Emory’s is on the eccentric side. Dooley made his first appearance in 1899 in the “Phoenix,” Emory’s literary journal at the time, with an essay titled “Reflections of the Skeleton.” Writing as a specimen from the Science Room, Dooley was a mournful character, complaining about the high spirits of the “college boys” who disturbed his rest.

He showed up again a decade later and remained a kind of campus commentator, but his physical presence was not observed until 1941, when the Board of Trustees first allowed dancing on campus. That seems to have cheered him up.

Now known as James W. Dooley (he takes his first name and middle initial from the current university president), Dooley is represented on campus by a student – whose identity is kept secret – dressed as a skeleton in a black cape, a black top hat, and white gloves.

He has become a Lord of Misrule, the instigator of the festive Dooley’s Week – traditionally ushered in by the skeleton himself – who has arrived by helicopter, motorcycle and vintage car, accompanied by his entourage of student bodyguards.

Dooley is part of the rich history that Emory is celebrating during its 175th anniversary year, including many major science milestones. During the past 10 years alone, Emory researchers have made 1,418 invention disclosures and applied for 968 patents. The university has seen 32 products reach the market and launched 55 start-up companies. Read more in Emory Magazine.

Are we turning Steve Jobs into a saint?

Is that a MacBook Air Steve Jobs is presenting to the masses, or a bible for the cult of mass celebrity? (Photo credits, above and below: iStockphoto.com.)

Gary Laderman, chair of religion at Emory, writes on CNN's Belief Blog:

Steve Jobs has been the object of numerous memorials, and tributes - more than a million - are being posted on Apple’s “Remembering Steve” webpage, with condolences as well as testimonials about how Jobs and his products have touched and indeed transformed the lives of countless individuals.

Make no mistake about it, the veneration we are seeing in the aftermath of Jobs’ death is religious through and through - not “kinda” religious, or “pseudo” religious,” or “mistakenly” religious, but a genuine expression for many of heartfelt sacred sentiments of loss and glorification.

It is not tied to any institution like a church or to any discrete tradition like Buddhism; it is, instead, tied to a religious culture that will only grow in significance and influence in the years ahead: the cult of celebrity.


As more and more people move away from conventional religions and identify as “nones” (those who choose to claim “no religion” in polls and surveys), celebrity worship and other cultural forms of sacred commitment and meaning will assume an even greater market share of the spiritual marketplace.

In life Jobs may have been something of an enigma who maintained his privacy and generally stayed out of the public limelight. In death, Jobs now is an immortal celebrity whose life story, incredible wealth, familiar visage, and igadgets will serve as touchstones for many searching for meaningful gods and modes of transcendence.

It has been said that death is the great equalizer - rich and poor, successes and failures, the powerful and the disempowered cannot escape the one inevitable fact of human existence.

Jobs and other celebrities cannot escape this reality, but unlike you and me, they live on in the memories of fans and followers and become guiding lights in the mundane darkness of our ordinary lives.

Read more on the CNN Belief Blog.

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Dalai Lama leads talks on ecology and ethics

“The slow meltdown of Earth’s capacity to sustain much of life, as we know it, poses an urgent challenge for both spiritual traditions and science.”

That’s the introductory statement to the conference on Ecology, Ethics and Interdependence, held Oct. 17-21 in Dharamsala, India. The Dalai Lama, Presidential Distinguished Professor at Emory, led the meeting, hosted by the Mind and Life Institute.

Emory religion scholar John Dunne moderated a session called “A Role for Theology," which is summed up on the conference web site:

“If our world view is one based on contemporary science as well as the deepest wisdom of many religions, a world view that claims we are radically interrelated and interdependent with all other forms of life, then we will, or should, respond to our present crisis with similarly radical changes in our thinking and behavior. But do we? This is the critical question for all fields of concern with climate change, including the religions – and it is a very difficult one. What causes people to change at a deep enough level so their behavior changes as well? The shock of climate change may be the catalyst to awaken us from the lie of the current world view of individual fulfillment through consumerism, to the reality of fulfillment by sharing with needy fellow creatures and the Earth itself, through religious understandings of limitation, detachment and self-emptying.”

The video of the session is above. Here's a link to videos of all the sessions of the conference.

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Happy Mole Day!

If you have to ask, chances are you are not celebrating Mole Day, an unofficial holiday for chemists, on October 23, between 6:02 AM and 6:02 PM. The time and date are based on Avogadro's number, which defines the number of particles in one mole of substance. Emory chemists celebrate in a big way. Their tradition involves a pinata, this year hand-crafted into an actual garden-variety mole by Charlene Chan and Yoshie Narui, and some initiation rites for new faculty members (see Chris Scarborough in action in the video below). Cheers to Avogadro, and to scientists everywhere today.