Technique permits convenient, precise optical imaging of individual proteins


September 22, 2020

Often considered the workhorses of the body, proteins are among the most important biomolecules critical to life processes. They provide structural foundation for cells and tissues and perform a dizzying array of tasks, from metabolizing energy and helping cells communicate with one another to defending the body from pathogens and guiding cell division and growth.

Because protein dysfunction is implicated in so many serious diseases, proteins are the primary targets for most therapeutic drugs. Shaopeng Wang is a researcher in the Biodesign Center for Bioelectronics and Biosensors. Download Full Image

In a new study, Arizona State Universisty Research Professor Shaopeng Wang and his colleagues describe a method for examining proteins in keen detail. To do this, his group makes clever use of a phenomenon known as surface plasmon resonance (SPR), incorporating it into an innovative type of microscope.

While SPR has been a powerful technique for investigating the world of the very small, including the interactions of bacteria and viruses, the study marks the first occasion when SPR has successfully been used to image single molecules, in this case, proteins. The new method is known as plasmon scattering microscopy.

According to Wang, “the race to develop this technology actually started 20 years ago.”

Along with lead author NJ TaoNJ Tao, directed the Biodesign Center for Bioelectronics and Biosensors, prior to his unexpected death in March of this year. He was a leading figure in the advancement of techniques for nanoscale measurements in areas including molecular electronics, optical imaging and biosensing., the group calculated that a modified form of SPR should have the sensitivity to resolve single proteins, though much preparatory work was required to make this a reality.

Wang is a researcher in the Biodesign Center for Bioelectronics and Biosensors. The new research appears in the advanced online addition of the journal Nature Methods. Pengfei Zhang, a postdoc in the center, is the lead author of the paper.

Using SPR allows researchers to investigate the dynamics of cell surface proteins — primary targets for drug design — which are particularly challenging to observe using X-ray crystallography or NMR spectroscopy, the two conventional techniques usually brought to bear to characterize proteins.

But what is a surface plasmon?

“One property of metal is that you have a lot of free electrons,” Wang said, referring to electrons not bound to atoms. “When the condition of incident light on these electrons is just right, the energy in the light causes these electrons to resonate. These oscillating electrons produce a wave across the metal surface. This is surface plasmon resonance.”

When protein molecules (purple) bind to immobilized receptor molecules, (like the Y-shaped antibodies affixed to the slide surface), the refractive index at the gold surface changes, altering the surface plasmon resonance condition, and producing an increase in signal intensity. Graphic by Shireen Dooling

In order to detect the binding of an analyte molecule (like a protein) to a receptor molecule using SPR, the receptor molecule is usually immobilized on the sensor surface and the analyte molecule is added to an aqueous solution. Polarized light is typically directed under surface of a thin gold film, where surface plasmons are generated at a particular angle of the incident light. The surface confinement of light by the surface plasmon is seen as a decrease in intensity of reflected light.

When protein molecules bind to immobilized receptor molecules, the refractive index at the gold surface changes, altering the surface plasmon resonance condition and producing an increase in signal intensity. 

To refine and calibrate the system, the researchers first observed binding events using polystyrene nanoparticles, whose size can be precisely controlled. The nanoparticles also have the advantage of producing higher contrast, aiding their detection by SPR. Using smaller and smaller nanoparticles allowed the group to reach the tiny dimensions of a biological protein.

To achieve such impressive resolution, the researchers used a variant of the SPR technique, detecting light on the protein binding events from above, rather than below, which dramatically eliminates background noise, producing a crisp image. Because bound proteins scatter the SPR light in all directions, detection from the top avoids the reflected light, greatly improving image quality. 

Wang likens the effect to seeing stars against the background curtain of darkness, whereas stars are invisible to the eye against the noisy background of daylight. Detection of single proteins can be realized without a very powerful light source, since SPR produces strong enhancement to the light field near the sensor surface, clarifying the protein signal.

By homing in on protein binding affinity, one of the key parameters critical for the design of safer, more effective drugs, the new SPR technique should have a bright future in the biomedical arena as well as shedding new light on foundational issues at the molecular scale.

Richard Harth

Science writer, Biodesign Institute at ASU

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ASU center 'mixes it up' with virtual art exhibit honoring National Hispanic Heritage Month


September 22, 2020

The Hispanic Research Center at Arizona State University is home to an extensive collection of work by Hispanic artists. Over the years, the center has showcased this collection through a variety of in-person art shows, exhibitions and tours. Now, for the first time in its 35-year history, the center has launched a virtual art exhibit highlighting the work of artists of Mexican descent. 

Founded in 1985, the Hispanic Research Center is a research unit of The College of Liberal Arts and Sciences that serves the university and broader community through its academic exploration and distribution of resources in areas of importance to Hispanic culture.  "The Return to Aztlan," Alfredo Arreguín. Oil on canvas, 2005. Image courtesy of the Hispanic Research Center. Download Full Image

Jean Andino, interim director of the Hispanic Research Center and associate professor in the School for Engineering of Matter, Transport and Energy, said center staff were motivated to find new and engaging ways to make artwork from their collection accessible.

“Obviously in this time of COVID-19 things are a little bit different than they normally would be,” Andino said. “But we're so excited about the possibility of doing a lot more with the community and I’m encouraged by the enthusiasm that exists within the team.”

The virtual tour, titled “Mixing it Up,” features 12 videos narrated by Santiago Moratto, senior research specialist, and produced by Brandon Ortega, media specialist. In each video, Moratto gives a brief description of the work and shares context about the artist and subject matter. The exhibit showcases 10 pieces from the collection that were specially selected to celebrate and honor National Hispanic Heritage Month.

Each artwork depicts themes involving United States’ Hispanic identity including immigration, spirituality, traditional food and drink, and farmworker iconography. These themes are meant to provoke thought and discussion of social issues that are prevalent in present U.S. society. 

Andino said “Mixing it Up” is the first of many virtual art exhibits, with plans to curate more in the coming months. Aside from virtual art exhibits, the center is involved in a number of other projects across the university. With the recent passing of Gary Keller, the center’s longtime director, Andino was appointed interim director. She said she and the team remain determined to move ongoing projects forward while expanding the center’s reach. 

“Ultimately, when we start talking about social justice and social equity, it's crucial to have organizations that are able to speak to the needs of the community,” Andino said. “The Hispanic Research Center has the ability to bring diverse voices into the discussion and if you're trying to develop solutions for society, it's important to have all voices represented. We're always looking for new ideas and new opportunities to do collaborative work that will really impact the Hispanic community and the community in general.”

One of the center’s largest efforts is the Bilingual Press, a publisher that has produced literary works, scholarship and art books by or about Hispanics in the U.S. since 1973. The Bilingual Press has a catalog of 200 books authored by both established and emerging writers in English, Spanish and bilingual formats. 

In addition to the Bilingual Press, the center also leads the Western Alliance to Expand Student Opportunities, a regional alliance of community colleges, four-year colleges and universities that seeks to expand opportunities for students in Arizona, Colorado and Utah. The program specifically focuses on enhancing and diversifying student inclusion in science, technology, engineering and mathematics (STEM).

As an Afro-Latina woman in STEM, Andino said she feels passionate about the center’s work and hopes its efforts will lead to creating a more culturally diverse, accepting community.

“It’s critically important to have an organization like the Hispanic Research Center that is meant to provide some additional knowledge, especially in this day and age, so that we can all better understand how to interface with each other. The Hispanic population is such a diverse group of individuals — the center represents these different cultures and allows their voices to be heard.”

Emily Balli

Communications Specialist and Lead Writer, The College of Liberal Arts and Sciences