Biohybrid swimmers at low Reynolds number powered by tissue-engineered neuromuscular units

Aydin, Onur

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https://hdl.handle.net/2142/113801 Copy

Description

Title

Biohybrid swimmers at low Reynolds number powered by tissue-engineered neuromuscular units

Author(s)

Aydin, Onur

Issue Date

2021-09-01

Director of Research (if dissertation) or Advisor (if thesis)

Saif, M. Taher. A.

Doctoral Committee Chair(s)

Saif, M. Taher. A.

Committee Member(s)

• Bashir, Rashid
• Gazzola, Mattia
• Kong, Hyunjoon
• Rhodes, Justin S

Department of Study

Mechanical Sci & Engineering

Discipline

Mechanical Engineering

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• biohybrid
• swimmer
• low Re
• low Reynolds number
• locomotion
• NMJ
• neuromuscular junction
• neuromuscular unit
• motor unit
• flagellum
• flagella
• slender body

Abstract

Biohybrid machines are engineered systems which are built by integrating biological cells with synthetic materials and components. Development of biohybrid machines utilizes the classical engineering modalities of design, modeling, prototype fabrication, testing, and iteration, but also draws from a toolbox that includes biological cells and materials. This enables a range of exciting possibilities since biological systems can develop via self-organization, function autonomously, and monitor and adapt to their environments. Pioneering studies on biohybrid machines have demonstrated the development of devices powered by muscle cells, capable of locomotion, pumping, and micromanipulation. A currently emerging frontier in the field is the integration of neuronal control. A wide range of complex animal behaviors are orchestrated by the nervous system which interfaces the body with the environment through sensing, information processing, and coordinating motor activity. Hence, the integration of neurons may enable the development of autonomous biohybrid machines capable of higher-level functionalities such as sensing, memory, and adaptation. The focus of this dissertation is on the implementation of neuronal actuation in muscle powered biohybrid machines. Firstly, we develop an experimental bioactuator platform to study the in vitro development of neuromuscular units. Engineered skeletal muscle tissues, anchored to compliant pillars, are co-cultured on the platform with optogenetic stem cell-derived neuronal clusters containing motor neurons. The motor neurons extend axons and innervate the muscle fibers, forming functional neuromuscular units. Our study illustrates several outcomes of synergistic interactions between the muscles and neurons. Muscles co-cultured with neurons exhibit significantly higher contraction force and cytoskeletal maturation compared to muscles cultured alone. Neurons self-organize into networks which generate synchronous bursting patterns, the development of which is facilitated by muscle-secreted soluble factors. Next, we implement our neuron-muscle co-culture approach on a free-standing compliant scaffold containing slender flagella, to demonstrate the first example of a biohybrid swimmer powered by neuromuscular units. Optogenetic stimulation of motor neurons evokes periodic muscle contractions, and the swimmer is driven by the resulting time-irreversible deformations of the flagella, a common mechanism of propulsion at low Reynolds number. Lastly, we investigate potential design strategies for improving swimming performance, assisted by analytical and computational models. Our models predict that the swimming speed of our initial prototype can be improved by up to two orders of magnitude by redesigning the swimmer scaffold to reduce drag and increase actuation amplitude.

Graduation Semester

2021-12

Type of Resource

Thesis

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http://hdl.handle.net/2142/113801

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Copyright 2021 Onur Aydin

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