Printed Motion: Holding Molecular Movement

Printed Motion: Holding Molecular Movement 150 150 Katie Brind'Amour, PhD, MS, CHES

When student researcher Shareef Dabdoub discovered the appealing aesthetics of a transcriptional regulator from the Streptococcus family, he knew that cellular biology had handed him a work of art. And by using a computer program to predict the 3-D configuration of the molecule and its most probable pathway for rearranging from one state to another, he observed molecular poetry in motion. Then his faculty advisor, William C. Ray, PhD, took the process one step further: He turned that motion into a physical model he could hold in the palm of his hand.

The advent of 3-D printers in the 1980s enabled the handling and study of precise physical models of proteins and cells. Now, researchers like Dr. Ray can combine the idea of digital time-lapse motion prediction with an actual printed model of that motion — allowing other researchers to study the molecule’s movement by working with a hand-held model. This use of 3-D printing technology could yield new insights about molecular motion involved in disease processes and cellular function, says Dr. Ray, principal investigator in the Battelle Center for Mathematical Medicine in The Research Institute at Nationwide Children’s Hospital.

“I can watch a 3-D image move in stop-motion on the computer screen and think, ‘Yes, I understand this molecule’s movement,’” says Dr. Ray, who advised Dabdoub during the student’s graduate research at Nationwide Children’s. “But printing out a physical model that shows the time-lapsed motion of how the molecule gets from one configuration to the other gives a whole new level of insight. I am always surprised at how much more I can learn from holding the data in my hand.”

Dr. Ray’s lab is the first known group to study molecular motion using time-lapse images on screen and in 2-D printed form. And now, the Streptococcus segment has become the first printed 3-D model of such molecular motion. The long, thin lines of the model illustrate the paths traced over time by an iron-dependent transcriptional regulator — common to multiple members of the Streptococcus family — as it rearranges from an inactive state (in blue) to its active state (in yellow).

While still an emerging field, molecular motion appears to have a large effect on molecular function. Many modern drugs work by effectively jamming the “lock and key” mechanisms that disease-causing molecules use to access their target cells. Understanding how a molecule’s motion is linked to its function makes it possible to consider treatments that essentially block the door of infection or disease, even if the lock isn’t jammed.

“These printers could be used to print any sort of molecular motion model to help scientists study the way proteins rearrange or viral vectors transform when they meet a host,” Dr. Ray explains. “It offers scientists studying anything molecular a whole new way of visualizing and conceptualizing the life of the molecules they study.”

When Dabdoub, now a postdoctoral researcher at The Ohio State University College of Dentistry, first visualized this regulator on-screen, the digital model was enough to captivate Dr. Ray and his team. Now, the concept of printed motion may become the lab’s new standard.

“There is definitely something to be said for handling this type of model,” Dr. Ray says. “I can see potential for this in everything from adeno-associated viral vector studies, where the technique has already helped us understand how to make improved vectors, to designing more efficient and stable enzymes to process biofuels.”

The study of molecular motion could also bring scientists closer to a novel treatment for respiratory syncytial virus (RSV) by allowing the study of the dramatic change the virus undergoes to begin infecting healthy cells, Dr. Ray says. If the viral molecular motion is understood and the transformation is blocked, RSV could be rendered innocuous.

About the author

Katherine (Katie) Brind’Amour is a freelance medical and health science writer based in Pennsylvania. She has written about nearly every therapeutic area for patients, doctors and the general public. Dr. Brind’Amour specializes in health literacy and patient education. She completed her BS and MS degrees in Biology at Arizona State University and her PhD in Health Services Management and Policy at The Ohio State University. She is a Certified Health Education Specialist and is interested in health promotion via health programs and the communication of medical information.