Date of Award
Fall 12-20-2024
Level of Access Assigned by Author
Open-Access Thesis
Degree Name
Master of Science (MS)
Department
Biological Engineering
Advisor
Rosemary L. Smith
Second Committee Member
Gregory Cox
Third Committee Member
Karissa Tilbury
Abstract
Human locomotion is the result of precisely coordinated processes between two interdependent tissues: nerve and muscle. Intertwined morphogenic signals that vary in space and time, autonomously driven cellular responses, and electrical/mechanical inputs play a role in the carefully orchestrated dance that takes place during neuromuscular tissue development. A consequence of this complex process is multiple means through which normal development can be disrupted, resulting in neuromuscular disease. Furthermore, these intricacies pose challenges for researchers trying to identify the causes of such diseases or to characterize the processes required for normal development. Traditional methods and tools, such as model organisms and tissue culture, have long been effective in parsing out many of the details, particularly regarding each tissue’s independent developmental processes. These methods continue to be invaluable in expanding our understanding, such as a detailed understanding of the specific morphogens and mechanisms of communication particular to motor neurons and muscles, and form the basis upon which new experimental techniques, such as the one presented here, are derived.
Here, we present an innovative, microfabricated 3D co-culture platform that blends many of the dynamic aspects of the in vivo environment with the ease and control of an in vitro model system. This device allows for the independent development of stem cells into two cell types, by providing each with its individual complexity of requisite morphogens while simplifying the communicative landscape between the cells to interconnecting microchannels. This unique tissue culturing method enables us to probe neuromuscular specific, paracrine cell-cell signaling pathways that contribute to a wider network of signals from other tissues within the developing organism. This thesis works toward characterizing neuromuscular network formation within the device, to open avenues for investigations into disease modeling, nerve-muscle pairing, and motor neuron subtype specification. This is completed through three aims:
(1) Optimizing the yield and assembly of microdevices.
(2) Enhancing the development of motor neurons and myoblasts.
(3) Establish methodologies to assess the presence and functionality of neuromuscular junctions.
Together, these progress the project toward forming functional neuromuscular circuitry on-chip.
Recommended Citation
Bell, Kailey E., "A Microengineering Approach to Modeling Neuromuscular Development" (2024). Electronic Theses and Dissertations. 4109.
https://digitalcommons.library.umaine.edu/etd/4109
Comments
Video referenced in section 5.2.2 (Figure 24): https://www.youtube.com/watch?v=8JCUcRQafKc
Video referenced in section 5.2.5: https://www.youtube.com/watch?v=ouDPbLigrwk