Biocomponent Devices: Developing Actuators from Insect Muscles

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All human-made devices, from the very first pre-historic tools to present day robots, have been constructed from non-living materials, most of which are very stiff and synthetic. To make modern devices more suitable for use in close proximity to humans and for work in natural environments it is important that we find new ways to build machines that are biologically compatible, biodegradable, environmentally safe and able to interface with tissues. A major challenge for making such biologically compatible machines is that there are no suitable motors (actuators) to make them move. Attempts to use muscle cells derived from animals such as frogs and mice have had limited success because vertebrate tissues require an intricate blood system and they are easily damaged by changing environmental conditions. It is also hard to replicate the conditions found in a vertebrate embryo that make muscles grow appropriately. This research introduces a new biological approach to making such actuators by growing them from insect cells produced during metamorphosis. Adult insect tissues (such as flight muscles) form directly on existing larval tissues and their growth can be controlled using simple manipulations of insect hormones. Preliminary studies show that insect muscles can be grown in culture at room temperature and that they will survive for many months. This research will identify the conditions needed to generate powerful insect muscles and develop methods to grow them for use in living machines. Successful completion of this work will lead to the production of an engineered muscle that can be sustained for several months and that can generate forces ten times greater than current muscle actuators grown in culture. The work will have wider implications in revealing some of the processes (genetic, biochemical and hormonal) that lead to the re-programming of cells that must occur as part of insect metamorphosis. This is expected to stimulate new experimental approaches to studies of tissue specification, growth and repair. These studies will test the hypothesis that fully formed tissues can be grown ex-vivo from metamorphic cells of the tobacco hawk moth Manduca sexta. Using the dorsal longitudinal (flight) muscles (DFM) as a target tissue the experiments will focus on four main goals: 1) To characterize the physiological and molecular changes that accompany DFM formation during metamorphosis and in culture. Measurements will be made of in vivo changes in electrical characteristics and the contractile properties using isometric/isotonic tests and dynamic work loops. The gene expression profile (transcriptome) of developing muscles and growing explants will be compared at different stages to help identify gene networks associated with Manduca muscle formation. 2) To characterize the roles of local (cell-cell, mechanical) and systemic (circulating) factors in muscle specification, differentiation and growth. This will involve tissue excision and cross stage transplant methods that are well established for insects. 3) To recapitulate the normal formation of adult dorsal flight muscles from larval precursors in culture by engineering the hormonal and substrate conditions. The transcriptomes of the in-vitro muscles will be compared with both native larval and adult DFMs to look for changes in key developmental and physiological gene networks. 4) To grow and maintain muscle constructs in-vitro for practical actuator applications. The goal is to engineer a muscle that can be sustained for several months and that can generate stress an order of magnitude better than current in-vitro muscle actuators by maximizing survival, cell proliferation and eventual differentiation. It is expected that this process will produce densely packed muscle fibers that can be used for high-stress actuators. The unified contraction of these fibers will be controlled by growing them on micro-electrode arrays or though the expression of light-sensitive channels such as ChR2. This research will engage graduate students in cross-disciplinary research in soft robotics.