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Biocomponent Devices: Developing Actuators from Insect Muscles

生物组件设备：利用昆虫肌肉开发执行器

基本信息

批准号：
1557672
负责人：
Barry Trimmer
金额：
$ 61.67万
依托单位：
Tufts University
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2016
资助国家：
美国
起止时间：
2016-05-15 至 2021-04-30
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1557672&HistoricalAwards=false
关键词：
Biocomponent Devices Developing Actuators Insect

项目摘要

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.

所有的人造设备，从最早的史前工具到今天的机器人，都是由非生命材料制成的，其中大多数都是非常坚硬和合成的。为了使现代设备更适合在人类附近使用，并在自然环境中工作，我们必须找到新的方法来制造生物相容，可生物降解，环境安全并能够与组织接触的机器。制造这种生物相容性机器的主要挑战是没有合适的马达（致动器）使它们移动。尝试使用来自青蛙和小鼠等动物的肌肉细胞取得了有限的成功，因为脊椎动物组织需要复杂的血液系统，并且它们很容易因环境条件的变化而受损。在脊椎动物胚胎中发现的使肌肉适当生长的条件也很难复制。这项研究介绍了一种新的生物学方法，通过从昆虫变态过程中产生的细胞中生长出这种致动器。成虫组织（如飞行肌）直接在幼虫组织上形成，它们的生长可以通过简单的昆虫激素控制。初步研究表明，昆虫的肌肉可以在室温下培养，并且可以存活数月。这项研究将确定产生强大的昆虫肌肉所需的条件，并开发出将其用于活体机器的方法。这项工作的成功完成将导致工程肌肉的生产，可以持续几个月，并可以产生比目前在培养中生长的肌肉致动器大十倍的力。这项工作将在揭示一些导致细胞重新编程的过程（遗传，生物化学和激素）方面产生更广泛的影响，这些过程必须作为昆虫变态的一部分发生。预计这将刺激新的实验方法来研究组织的规格，生长和修复。这些研究将测试的假设，完全形成的组织可以离体生长的变态细胞烟草天蛾。使用背纵（飞行）肌（DFM）作为靶组织，实验将集中在四个主要目标：1）表征在变态和培养过程中伴随DFM形成的生理和分子变化。将使用等长/等张试验和动态工作循环测量电特性和收缩特性的体内变化。发育中肌肉和生长中外植体的基因表达谱（转录组）将在不同阶段进行比较，以帮助确定与Manduca肌肉形成相关的基因网络。2)描述肌肉特化、分化和生长中局部（细胞-细胞、机械）和系统（循环）因素的作用。这将涉及组织切除和跨阶段移植方法，这些方法已经为昆虫建立了良好的基础。3)通过调节激素和底物条件，重现培养中幼虫前体的成体背飞行肌的正常形成。将体外肌肉的转录组与天然幼虫和成虫DFM进行比较，以寻找关键发育和生理基因网络的变化。4)在体外生长和维持肌肉结构，以用于实际的致动器应用。其目标是设计一种可以持续数月的肌肉，并且可以通过最大化存活，细胞增殖和最终分化来产生比目前体外肌肉致动器更好的数量级的应力。预计这一过程将产生密集的肌肉纤维，可用于高应力致动器。这些纤维的统一收缩将通过在微电极阵列上生长它们或通过表达光敏通道如ChR 2来控制。这项研究将使研究生从事软机器人的跨学科研究。