Understanding the mechanical biology of life's bonds

Dec 23, 2011 By Beth Kwon

(PhysOrg.com) -- When he was 10 years old, Julio Fernandez took a correspondence course in electronics and earned a certificate for putting together a doorbell. Today, the Columbia professor of biological sciences builds and takes apart proteins, the building blocks of the body which, when they bond improperly, may cause disease.

Traditionally, scientists study proteins in a test tube, a method that Fernandez believes does not offer an accurate enough picture of complex body biochemistry. “In a how would you know what’s happening to something that requires mechanical force to extend and relax?” he says, referring to the stretching and contracting that happens to proteins when they bond with one another in the body. “You have to study proteins and biological molecules in an environment as close to their native condition as possible.”

To that end, Fernandez has spent his career developing a new field—mechanical biology—to understand organic substances with tools from physics, engineering and computer science. His team in the Northwest Corner building builds its own equipment, engineers its own proteins and writes its own computer programs to analyze the data. Though the students each have academic specialties, many have picked up expertise on the job in other disciplines.

In a paper published in the October edition of Nature Chemistry, Fernandez’s team made the first direct observation of how disulfide bonds reshuffle within a . Disulfide bonds play a central role in controlling the elasticity of tissues. They used an atomic force microscope, a device developed by physicists in the 1980s to study items such as computer chips at the nanoscale, but adapted by his team to examine biological substances.

“Think of a protein as a rope tied up in a knot that is held together by a disulfide bond,” explains Pallav Kosuri, a Ph.D. student on Fernandez’s team. “Someone breaks the disulfide bond and the knot can now unfurl. We’re watching knots unfurl in a single protein molecule.” The team placed proteins on the examining surface of the atomic force microscope, which is fitted with a sensitive tip that is more than a thousand times sharper than the thickness of a human hair. The tip is attached to the protein, and a laser is used to record the exact position of the tip as the knot unfurls—or when the protein bonds reshuffle.

Disulfide bonds occur in nearly 30 percent of proteins; because they’re so prevalent, scientists believe their interactions may be clues to unraveling a broad range of illnesses, from infectious disease to cancer. Viruses, for example, interact with human cells through proteins that contain disulfide bonds. Marfan Syndrome is a disorder in which fibrillin, a disulfide-bonded protein in connective tissue, malfunctions. Symptoms may include extraordinarily stretchy skin, and in heart tissue, a faulty elasticity that can affect healthy blood flow.

As a physics student at the University of Chile, Fernandez met a group of neuroscientists from Los Angeles studying a squid native to the shores of that South American country. They lured Fernandez to the UCLA School of Medicine, where he received his Ph.D. in physiology and was a post-doctoral research fellow. Following appointments at the Max Planck Institute, the University of Pennsylvania’s School of Medicine and the Mayo Foundation, Fernandez came to Columbia in 2002.

His lab is currently at work studying how muscle elasticity works. They’re also trying to understand the elasticity of the main receptor implicated in HIV infection—another protein with disulfide bonds. “We’re trying to revolutionize protein biochemistry from the point of view of mechanical forces,” he says.

Explore further: Cells build 'cupboards' to store metals

add to favorites email to friend print save as pdf

Related Stories

Scientists pioneer new method for watching proteins fold

Dec 22, 2011

(PhysOrg.com) -- A protein’s function depends on both the chains of molecules it is made of and the way those chains are folded. And while figuring out the former is relatively easy, the latter represents ...

The molecular force is with this team

Oct 26, 2011

Xiaohui “Frank” Zhang is integrating physics, immunology and biology to develop a “nanodevice” that could provide a new treatment for stroke, thrombosis and atherosclerosis.

Recommended for you

Cells build 'cupboards' to store metals

Dec 17, 2014

Lawrence Livermore researchers in conjunction with collaborators at University of California (link is external), Los Angeles have found that some cells build intracellular compartments that allow the cell ...

Stunning zinc fireworks when egg meets sperm

Dec 15, 2014

Sparks literally fly when a sperm and an egg hit it off. The fertilized mammalian egg releases from its surface billions of zinc atoms in "zinc sparks," one wave after another, a Northwestern University-led ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.