A Tale of Castles, Collagen
and Chemistry
Nancy Forde | Simon Fraser University
When Nancy Forde swings a hockey stick, she knows how the puck will behave
under the force. It’ll fly. Her newest research will show how a single
molecule, the kind in a tendon’s collagen, will behave under the
force of laser light applied in her lab.
She once played pickup hockey in Toronto, then in Chicago in her Ph.D. years, and she’d be playing yet but for two concerns: a 1-year-old daughter, Gillian, and her expanding work under a new Research Corporation award for single-molecule techniques in biological physics at Simon Fraser University near Vancouver.
Magnetic tweezers utilize a magnetic field gradient to manipulate micron-sized paramagnetic objects. A schematic of the experimental set-up is shown in the figure to the right. The molecule of interest is tethered between a micron-sized sphere and a surface. The molecule is stretched by the magnetic force acting on the tethered bead, and by rotating the magnetic field (and hence the paramagnetic bead), torque can be applied to twist the molecule.
For now, she’s content with memories of Monday night hockey with other scientists in the San Francisco Bay area, the best place to find some ice while learning biophysics during a post doc at Berkeley and starting to use molecular-level “tweezers.”
Her work now focuses on how force alters the behavior of molecules, using the collagen that forms our bones, tendons, skin, cartilage and teeth. Her work may reveal how tissues deteriorate with age, and may fill gaps in knowledge of cancer and diabetes. To study those molecules, she has built a version of the devices called optical and magnetic tweezers that can unfurl a single strand of collagen’s triple helix. Her instruments can exert tiny forces — from one to 100 picoNewtons — on the collagen.
“We want to grab it, pull on it, stretch it, measure the forces; grab it by its ends, and pull and twist it,” she said.
The strands of protein measure only 300 or so billionths of a meter, way too small to be actually grabbed. So a molecule is first caught between tweezers tips a millionth of a meter wide. By sticking each end of the molecule to a bead, and pulling the beads apart, she can stretch the molecule. By twisting one of the molecules, she can “wind” it up. She manipulates the beads using optical forces from a focused laser beam or magnetic forces from a pair of magnets (like ones found at Radio Shack).
She gauges the resistance between the beads, and checks their length, using low-resolution mode video microscopy. In high-resolution mode, she can measure by deflection of the laser beam by the trapped bead.
This work involves approaches from a variety of disciplines: physics, chemistry and molecular biology. Where she works, in the Shrum Science Building at Simon Fraser, on top of Burnaby Mountain, all the sciences are interconnected. Her research group includes people from physics, chemistry, biochemistry and biology, all working together to help slice one basic question: “How does the chemical structure of collagen determine its response to force and torque?”
That question is vital to understanding how such a protein — and by extension a tendon — will hold up and do its work.
Imagine a rope of many smaller threads inside an elbow. That’s one way to think of collagen, a bunch of tiny triple helical rods packed together to make the strong, stiff tendon that affords you mechanical stability as you, say, swing a hockey stick.
Forde’s team will, she says, “take a bottom up approach, starting with a single protein, understanding its reaction to force.” That’s one piece of the puzzle involving how the proteins, each with its own task, form a complex different system.
Then imagine you are about to build giant castle with a Lego set. If you could study how strong each block was, and in turn each bit of wall, you’d be following the approach of the Forde group toward knowledge of our own strengths and vulnerability — from single proteins to fibrils to tendons and bones, and the physics and chemistry that underlies it all.
“After decades of study, I’m fascinated by the open questions that still remain,” she said. “These single molecule techniques could reveal new answers to how much force will begin to change structures.”
Nov. 1, 2007
