Optogenetic skeletal muscle-powered adaptive biological machines

Abstract

Complex biological systems sense, process, and respond to their surroundings in real time. The ability of such systems to adapt their behavioral response to suit a range of dynamic environmental signals motivates the use of biological materials for other engineering applications. As a step toward forward engineering biological machines (bio-bots) capable of nonnatural functional behaviors, we created a modular light-controlled skeletal musclepowered bioactuator that can generate up to 300 μN (0.56 kPa) of active tension force in response to a noninvasive optical stimulus. When coupled to a 3D printed flexible bio-bot skeleton, these actuators drive directional locomotion (310 μm/s or 1.3 body lengths/min) and 2D rotational steering (2°/s) in a precisely targeted and controllable manner. The muscle actuators dynamically adapt to their surroundings by adjusting performance in response to "exercise" training stimuli. This demonstration sets the stage for developing multicellular bio-integrated machines and systems for a range of applications.bioactuator | stereolithography | tissue engineering | soft robotics U nderstanding complex biological systems requires uncovering the mechanisms through which integrated multicellular networks accomplish sensing, internal processing, and coordinated action in response to dynamic environmental signals. Attempting to reverse engineer these mechanisms for applications in regenerative medicine has been the focus of the burgeoning field of tissue engineering (1), and seminal advances in this field have targeted nearly every organ system in the body (2). These developments, in addition to improving the state of the art in therapeutics, have furthered our understanding of the design principles governing the organizational structure and function of natural biological systems. With this as a guide, we are ideally poised to start forward engineering biological machines, or bio-bots, capable of complex controllable nonnatural functional behaviors, thereby broadening the potential applications for building with biological materials.Before we can design bio-integrated machines for a range of applications, we must first engineer modular tissue building blocks that respond to external signals with complex functional behaviors. Observing and controlling the coordinated action of such building blocks in series and parallel will help us understand the emergent behavior of natural biological systems (3, 4). Nearly all machines require actuators, modules that convert energy into motion, to produce a measurable output in response to input stimuli. Efforts to manufacture bio-integrated actuators have targeted a range of cell types (5), including flagellated bacteria (6), cardiac muscle (7-9), and skeletal muscle (10-12). We previously demonstrated a millimeter-scale soft robotic device, or biobot, that uses the contractile force produced by electrically paced skeletal muscle to drive locomotion across a substrate (10). This bio-bot was the first demonstration of an untethered locomotive skeletal mu...

Untethered soft robotics

“…2c). These bio-hybrid systems can incorporate muscle tissue, such as those engineered from the C2C12 line of mouse myoblasts, directly into soft systems 17,45 . For these systems, actuation can be induced by applying electrical or optical impulses.…”

“…For these systems, actuation can be induced by applying electrical or optical impulses. These actuators show directional locomotion and can benefit from 'exercise' training, thus highlighting the ability of bio-hybrid machines to adapt to their environment 45 .…”

Biomimicry, Biofabrication, and Biohybrid Systems: The Emergence and Evolution of Biological Design

“…[120] Taking advantage of the precise spatiotemporal control over muscle contraction enabled by optogenetics, we showed that directional locomotion and 2D rotational steering could be accomplished in completely symmetric structures (Figure 10A). Additionally, we showed that an "exercise" regimen of daily optical stimulation significantly enhanced muscle force production, and coupling optical and mechanical stimulation led to a further synergistic increase in muscle performance.…”

A 3D-printed platform for modular neuromuscular motor units

“…The modularity of these subunits (consisting of cells, tissues, and biomaterials, along with growth factors or other biochemical signals) allows for "forward-engineering" of the system by assembling the components in a diverse manner, like building blocks, thus expanding the functionality of the system. For example, we recently demonstrated a modular skeletal muscle tissue "ring" that could be coupled to a three-dimensional (3D)-printed skeleton to produce net motion 2 . This bio-integrated actuator (bio-bot) was a functional cellular system that exhibited dynamic and adaptive behavior based on both its inherent design and its surroundings.…”