Scientists have long suspected that, like the strings on a violin or the pipes of an organ, the proteins in the human body vibrate in different patterns. A new study offers conclusive evidence that this is true.
Using a technique they developed based on terahertz near-field microscopy, researchers have for the first time observed in detail the vibrations of lysozyme, an antibacterial protein found in many animals.
The team found that the vibrations, which were previously thought to dissipate quickly, actually persist in molecules like the “ringing of a bell,” says Andrea Markelz, professor of physics at the University at Buffalo who led the study published in Nature Communications.
These tiny motions enable proteins to change shape quickly so they can readily bind to other proteins, a process that is necessary for the body to perform critical biological functions like absorbing oxygen, repairing cells, and replicating DNA. The research opens the door to a whole new way of studying the basic cellular processes that enable life.
“People have been trying to measure these vibrations in proteins for many, many years, since the 1960s. In the past, to look at these large-scale, correlated motions in proteins was a challenge that required extremely dry and cold environments and expensive facilities,” Markelz says.
“Our technique is easier and much faster. You don’t need to cool the proteins to below freezing or use a synchrotron light source or a nuclear reactor—all things people have used previously to try and examine these vibrations.”
The way a wine glass shatters
To observe the protein vibrations, Markelz’s team relied on an interesting characteristic of proteins: they vibrate at the same frequency as the light they absorb.
This is analogous to the way wine glasses tremble and shatter when a singer hits exactly the right note, Markelz says. Wine glasses vibrate because they are absorbing the energy of sound waves, and the shape of a glass determines what pitches of sound it can absorb.
Similarly, proteins with different structures will absorb and vibrate in response to light of different frequencies.
So, to study vibrations in lysozyme, the researchers exposed a sample to light of different frequencies and polarizations, and measured the types of light the protein absorbed.
This technique, developed with Edward Snell, assistant professor of structural biology and a senior research scientist at Hauptman-Woodward Medical Research Institute, allowed the team to identify which sections of the protein vibrated under normal biological conditions. They were also able to see that the vibrations endured over time, challenging existing assumptions.
Like a bell, not a wet sponge
“If you tap on a bell, it rings for some time, and with a sound that is specific to the bell. This is how the proteins behave,” Markelz says. “Many scientists have previously thought a protein is more like a wet sponge than a bell: If you tap on a wet sponge, you don’t get any sustained sound.”
The team’s technique for studying vibrations could be used in the future to document how natural and artificial inhibitors stop proteins from performing vital functions by blocking desired vibrations.
“We can now try to understand the actual structural mechanisms behind these biological processes and how they are controlled. The cellular system is just amazing,” she says.
“You can think of a cell as a little machine that does lots of different things—it senses, it makes more of itself, it reads and replicates DNA, and for all of these things to occur, proteins have to vibrate and interact with one another.”
Source: University at Buffalo