Optogenetic Skeletal Muscle Cells Activated by Light

Optogenetic Skeletal Muscle Cells Activated by Light

Scientists have been working with lab-grown muscle tissue for quite a while now, but the only way to trigger contractions has been electric stimulation. This requires wiring and electrodes that gently attach to tissue, and that complicates matters if you want to build something that’s powered by artificially created muscle cells.

Now researchers from MIT and the University of Pennsylvania used optogenetics to create engineered skeletal muscle cells that contract when illuminated by a 20-millisecond blue light beam. Previously cardiac cells were created using optogenetics, a technique that embeds genes that code for light reactive proteins, but the new development should be more useful in robotics and perhaps even in prostheses that will use light activated muscles made at a factory.

The light-sensitive muscle tissue exhibits a wide range of motions, which may enable highly articulated, flexible robots — a goal the group is now working toward. One potential robotic device may involve endoscopy, a procedure in which a camera is threaded through the body to illuminate tissue or organs. Asada [Harry Asada professor of engineering at MIT] says a robot made of light-sensitive muscle may be small and nimble enough to navigate tight spaces — even within the body’s vasculature. While it will be some time before such a device can be engineered, Asada says the group’s results are a promising start.

“We can put 10 degrees of freedom in a limited space, less than one millimeter,” Asada says. “There’s no actuator that can do that kind of job right now.”

Rashid Bashir, a professor of electrical and computer engineering and bioengineering at the University of Illinois at Urbana-Champaign, says the group’s light-activated muscle may have multiple applications in robotics, medical devices, navigation and locomotion. He says exploring these applications would mean the researchers would first have to address a few hurdles. “Development of ways to increase the forces of contraction and being able to scale up the size of the muscle fibers would be very useful for future applications,” Bashir says.

Many robotic designs take nature as their muse: sticking to walls like geckos, swimming through water like tuna, sprinting across terrain like cheetahs. Such designs borrow properties from nature, using engineered materials and hardware to mimic animals’ behavior.

Now, scientists at MIT and the University of Pennsylvania are taking more than inspiration from nature — they’re taking ingredients. The group has genetically engineered muscle cells to flex in response to light, and is using the light-sensitive tissue to build highly articulated robots. This “bio-integrated” approach, as they call it, may one day enable robotic animals that move with the strength and flexibility of their living counterparts.

The researchers’ approach will appear in the journal Lab on a Chip.

Harry Asada, the Ford Professor of Engineering in MIT’s Department of Mechanical Engineering, says the group’s design effectively blurs the boundary between nature and machines.

“With bio-inspired designs, biology is a metaphor, and robotics is the tool to make it happen,” says Asada, who is a co-author on the paper. “With bio-integrated designs, biology provides the materials, not just the metaphor. This is a new direction we’re pushing in biorobotics.”

Seeing the light

Asada and MIT postdoc Mahmut Selman Sakar collaborated with Roger Kamm, the Cecil and Ida Green Distinguished Professor of Biological and Mechanical Engineering, to develop the new approach. In deciding which bodily tissue to use in their robotic design, the researchers set upon skeletal muscle — a stronger, more powerful tissue than cardiac or smooth muscle. But unlike cardiac tissue, which beats involuntarily, skeletal muscles — those involved in running, walking and other physical motions — need external stimuli to flex.

Normally, neurons act to excite muscles, sending electrical impulses that cause a muscle to contract. In the lab, researchers have employed electrodes to stimulate muscle fibers with small amounts of current. But Asada says such a technique, while effective, is unwieldy. Moreover, he says, electrodes, along with their power supply, would likely bog down a small robot.

Instead, Asada and his colleagues looked to a relatively new field called optogenetics, invented in 2005 by MIT’s Ed Boyden and Karl Deisseroth from Stanford University, who genetically modified neurons to respond to short laser pulses. Since then, researchers have used the technique to stimulate cardiac cells to twitch.

Asada’s team looked for ways to do the same with skeletal muscle cells. The researchers cultured such cells, or myoblasts, genetically modifying them to express a light-activated protein. The group fused myoblasts into long muscle fibers, then shone 20-millisecond pulses of blue light into the dish. They found that the genetically altered fibers responded in spatially specific ways: Small beams of light shone on just one fiber caused only that fiber to contract, while larger beams covering multiple fibers stimulated all those fibers to contract.

A light workout

The group is the first to successfully stimulate skeletal muscle using light, providing a new “wireless” way to control muscles. Going a step further, Asada grew muscle fibers with a mixture of hydrogel to form a 3-D muscle tissue, and again stimulated the tissue with light — finding that the 3-D muscle responded in much the same way as individual muscle fibers, bending and twisting in areas exposed to beams of light.

The researchers tested the strength of the engineered tissue using a small micromechanical chip — designed by Christopher Chen at Penn — that contains multiple wells, each housing two flexible posts. The group attached muscle strips to each post, then stimulated the tissue with light. As the muscle contracts, it pulls the posts inward; because the stiffness of each post is known, the group can calculate the muscle’s force using each post’s bent angle.

Asada says the device also serves as a training center for engineered muscle, providing a workout of sorts to strengthen the tissue. “Like bedridden people, its muscle tone goes down very quickly without exercise,” Asada says.

The light-sensitive muscle tissue exhibits a wide range of motions, which may enable highly articulated, flexible robots — a goal the group is now working toward. One potential robotic device may involve endoscopy, a procedure in which a camera is threaded through the body to illuminate tissue or organs. Asada says a robot made of light-sensitive muscle may be small and nimble enough to navigate tight spaces — even within the body’s vasculature. While it will be some time before such a device can be engineered, Asada says the group’s results are a promising start.

“We can put 10 degrees of freedom in a limited space, less than one millimeter,” Asada says. “There’s no actuator that can do that kind of job right now.”

Rashid Bashir, a professor of electrical and computer engineering and bioengineering at the University of Illinois at Urbana-Champaign, says the group’s light-activated muscle may have multiple applications in robotics, medical devices, navigation and locomotion. He says exploring these applications would mean the researchers would first have to address a few hurdles. “Development of ways to increase the forces of contraction and being able to scale up the size of the muscle fibers would be very useful for future applications,” Bashir says.

In the meantime, there may be a more immediate application for both the engineered muscles and the microchip: Asada says the setup may be used to screen drugs for motor-related diseases. Scientists may grow light-sensitive muscle strips in multiple wells, and monitor their reaction — and the force of their contractions — in response to various drugs.

The other authors on the paper are Devin Neal, Yinqing Li and Ron Weiss from MIT, and Thomas Boudou and Michael Borochin from Penn.

This research was supported by the National Science Foundation, the National Institutes of Health, the RESBIO Technology Resource for Polymeric Biomaterials, the Center for Engineering Cells and Regeneration of the University of Pennsylvania, and the Singapore-MIT Alliance for Research and Technology.

Densely arrayed skeletal myotubes are activated individually and as a group using precise optical stimulation with high spatiotemporal resolution. Skeletal muscle myoblasts are genetically encoded to express light-activated cation channel, Channelrhodopsin-2, which allows for spatiotemporal coordination of the multitude of skeletal myotubes that contract in response to pulsed blue light. Furthermore, ensembles of mature functional 3D muscle microtissues have been formed from the optogenetically encoded myoblasts using a high-throughput device. The device, called “skeletal muscle on a chip”, not only provides the myoblasts with controlled stress and constraints necessary for muscle alignment, fusion and maturation, but also facilitates to measure forces and characterize the muscle tissue. We measured the specific static and dynamic stresses generated by the microtissues, and characterized the morphology and alignment of the myotubes within the constructs. The device allows for testing the effect of a wide range of parameters (cell source, matrix composition, microtissue geometry, auxotonic load, growth factors, and exercise) on the maturation, structure, and function of the engineered muscle tissues in a combinatorial manner. Our studies integrate tools from optogenetics and microelectromechanical systems (MEMS) technology with skeletal muscle tissue engineering to open up opportunities to generate soft robots actuated by multitude of spatiotemporally coordinated 3D skeletal muscle microtissues.

Source : http://web.mit.edu/newsoffice/2012/mechanical-engineers-create-light-activated-skeletal-muscle-0830.html

Related Posts Plugin for WordPress, Blogger...
Be Sociable, Share!

About the Author

has written 1822 posts on this blog.

Copyright © 2017 Medical Technology & Gadgets Blog MedicalBuy.net. All rights reserved.
Proudly powered by WordPress. Developed by Deluxe Themes