 Using a new imaging technique they developed, scientists have managed to observe and document the vibrations of lysozyme, an antibacterial protein found in many animals. This graphic visualizes the vibrations in lysozyme as it is excited by terahertz light (depicted by the red wave arrow). Such vibrations, long thought to exist, have never before been described in such detail, said lead researcher Andrea Markelz, a UB physicist. Credit: Credit: Andrea Markelz and Katherine Niessen. |
The strings on a violin or the pipes of an organ, the
proteins in the human body vibrate in different patterns, scientists have long
suspected. Now, a new study provides what researchers say is the first
conclusive evidence that this is true.
Using a technique they developed based on terahertz
near-field microscopy, scientists from the University at Buffalo and
Hauptman-Woodward Medical Research Institute (HWI) 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," said UB physics professor Andrea Markelz, PhD,
wh0 led the study.
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, Markelz said.
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," Markelz
said. "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."
"Our technique is easier and much faster,"
she said. "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 findings will appear in Nature Communications on
Jan. 16, and publication of information on the research is prohibited until 5
a.m. U.S. Eastern Time on that day.
To observe the protein vibrations, Markelz' team
relied on an interesting characteristic of proteins: The fact that 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 explained: 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, Markelz and her
colleagues 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, a senior
research scientist at HWI and assistant professor of structural biology at UB,
allowed the team to identify which sections of the protein vibrated under
normal biological conditions. The researchers were also able to see that the
vibrations endured over time, challenging existing assumptions.
"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 said. "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."
Markelz said 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," Markelz said.
"The cellular system is just amazing," she
said. "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."
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