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Investigating Mechanotransduction Behaviors of Natural and Engineered Molecular Sensors for Patient-Tailored Treatment Paradigms and Regenerative Rehabilitation- [electronic resource]
Investigating Mechanotransduction Behaviors of Natural and Engineered Molecular Sensors for Patient-Tailored Treatment Paradigms and Regenerative Rehabilitation- [electronic resource]
상세정보
- 자료유형
- 학위논문파일 국외
- 최종처리일시
- 20240214100454
- ISBN
- 9798379918095
- DDC
- 621
- 서명/저자
- Investigating Mechanotransduction Behaviors of Natural and Engineered Molecular Sensors for Patient-Tailored Treatment Paradigms and Regenerative Rehabilitation - [electronic resource]
- 발행사항
- [S.l.]: : Carnegie Mellon University., 2023
- 발행사항
- Ann Arbor : : ProQuest Dissertations & Theses,, 2023
- 형태사항
- 1 online resource(119 p.)
- 주기사항
- Source: Dissertations Abstracts International, Volume: 85-01, Section: B.
- 주기사항
- Advisor: LeDuc, Philip;Taylor, Rebecca.
- 학위논문주기
- Thesis (Ph.D.)--Carnegie Mellon University, 2023.
- 사용제한주기
- This item must not be sold to any third party vendors.
- 초록/해제
- 요약Living organisms respond to environmental cues by emitting signals. Mechanosensory physiology has been crucial for survival since the emergence of the first microorganisms 3.7 billion years ago. The ubiquitous and perpetual nature of mechanotransduction phenomena in all life forms underscores the importance of studying the fundamental mechanical responses that sustain and age us. In this thesis, we zoom in to the cellular scale to study calcium, the ion commonly regulated after mechanical loading in neural and muscle cells, and understand how their ion channels activate at different strain levels. We utilized neural cell-embedded cerebral organoids to gain insights into the effects of traumatic brain injury on the human brain. Additionally, we employed 3D stem cell-infused collagen scaffolds to analyze the differences in calcium signaling between young and aged muscle progenitor cells (MPCs) for regenerative rehabilitation purposes. Our findings revealed that fluorescent calcium signals and genetic pathways are triggered depending on the strain and strain rates of impact. Identifying genetic pathways after stimulation can help target gene products that have dire consequences in the cells to prevent activation or progression of disease, particularly in traumatic brain injury (TBI). Similarly, we can better understand the underlying mechanisms at play and develop potential interventions to improve cellular function in age-related disease. We obtained immediate cellular feedback via confocal microscopy and more detailed feedback via RNA sequencing from the mechanical insults imposed on the tested cellular systems.Furthermore, it is crucial to develop tools to measure these cellular forces at a molecular scale. To this end, we constructed programmable and highly tunable architectures for molecular scale measurement using DNA structures composed of single-stranded tiles (SSTs). We designed a micron scale DNA sensor to measure wall shear stress. One notable advantage of DNA-based probes is their ability to incorporate a broad range of functional customizations, such as fluorophores, biotin, and tags for protein conjugation. We leveraged this flexibility to nanopattern polymers onto DNA origami, creating extruded surfaces for novel biosensing. We fluorescently tagged the DNA nanosensor to output an optical signal indicating physical interactions between the probe and its environment. We also excluded the tag to visualize the predicted formation in atomic force microscopy.
- 일반주제명
- Mechanical engineering.
- 일반주제명
- Biomechanics.
- 일반주제명
- Molecular physics.
- 키워드
- Biosensing
- 키워드
- Nanosensor
- 기타저자
- Carnegie Mellon University Mechanical Engineering
- 기본자료저록
- Dissertations Abstracts International. 85-01B.
- 기본자료저록
- Dissertation Abstract International
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■00520240214100454
■006m o d
■007cr#unu||||||||
■020 ▼a9798379918095
■035 ▼a(MiAaPQ)AAI30492284
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a621
■1001 ▼aBeltran, Susana Maria.
■24510▼aInvestigating Mechanotransduction Behaviors of Natural and Engineered Molecular Sensors for Patient-Tailored Treatment Paradigms and Regenerative Rehabilitation▼h[electronic resource]
■260 ▼a[S.l.]:▼bCarnegie Mellon University. ▼c2023
■260 1▼aAnn Arbor :▼bProQuest Dissertations & Theses, ▼c2023
■300 ▼a1 online resource(119 p.)
■500 ▼aSource: Dissertations Abstracts International, Volume: 85-01, Section: B.
■500 ▼aAdvisor: LeDuc, Philip;Taylor, Rebecca.
■5021 ▼aThesis (Ph.D.)--Carnegie Mellon University, 2023.
■506 ▼aThis item must not be sold to any third party vendors.
■520 ▼aLiving organisms respond to environmental cues by emitting signals. Mechanosensory physiology has been crucial for survival since the emergence of the first microorganisms 3.7 billion years ago. The ubiquitous and perpetual nature of mechanotransduction phenomena in all life forms underscores the importance of studying the fundamental mechanical responses that sustain and age us. In this thesis, we zoom in to the cellular scale to study calcium, the ion commonly regulated after mechanical loading in neural and muscle cells, and understand how their ion channels activate at different strain levels. We utilized neural cell-embedded cerebral organoids to gain insights into the effects of traumatic brain injury on the human brain. Additionally, we employed 3D stem cell-infused collagen scaffolds to analyze the differences in calcium signaling between young and aged muscle progenitor cells (MPCs) for regenerative rehabilitation purposes. Our findings revealed that fluorescent calcium signals and genetic pathways are triggered depending on the strain and strain rates of impact. Identifying genetic pathways after stimulation can help target gene products that have dire consequences in the cells to prevent activation or progression of disease, particularly in traumatic brain injury (TBI). Similarly, we can better understand the underlying mechanisms at play and develop potential interventions to improve cellular function in age-related disease. We obtained immediate cellular feedback via confocal microscopy and more detailed feedback via RNA sequencing from the mechanical insults imposed on the tested cellular systems.Furthermore, it is crucial to develop tools to measure these cellular forces at a molecular scale. To this end, we constructed programmable and highly tunable architectures for molecular scale measurement using DNA structures composed of single-stranded tiles (SSTs). We designed a micron scale DNA sensor to measure wall shear stress. One notable advantage of DNA-based probes is their ability to incorporate a broad range of functional customizations, such as fluorophores, biotin, and tags for protein conjugation. We leveraged this flexibility to nanopattern polymers onto DNA origami, creating extruded surfaces for novel biosensing. We fluorescently tagged the DNA nanosensor to output an optical signal indicating physical interactions between the probe and its environment. We also excluded the tag to visualize the predicted formation in atomic force microscopy.
■590 ▼aSchool code: 0041.
■650 4▼aMechanical engineering.
■650 4▼aBiomechanics.
■650 4▼aMolecular physics.
■653 ▼aMechanotransduction
■653 ▼aTraumatic brain injury
■653 ▼aMuscle progenitor cells
■653 ▼aSingle-stranded tiles
■653 ▼aBiosensing
■653 ▼aNanosensor
■690 ▼a0548
■690 ▼a0648
■690 ▼a0609
■71020▼aCarnegie Mellon University▼bMechanical Engineering.
■7730 ▼tDissertations Abstracts International▼g85-01B.
■773 ▼tDissertation Abstract International
■790 ▼a0041
■791 ▼aPh.D.
■792 ▼a2023
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T16932410▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
■980 ▼a202402▼f2024
