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Using Mechanical Force to Study Biological Processes: From Blood Clotting to Immune Cell Adhesion- [electronic resource]
Using Mechanical Force to Study Biological Processes: From Blood Clotting to Immune Cell Adhesion- [electronic resource]
상세정보
- 자료유형
- 학위논문파일 국외
- 최종처리일시
- 20240214100427
- ISBN
- 9798379604530
- DDC
- 574.191
- 서명/저자
- Using Mechanical Force to Study Biological Processes: From Blood Clotting to Immune Cell Adhesion - [electronic resource]
- 발행사항
- [S.l.]: : Harvard University., 2023
- 발행사항
- Ann Arbor : : ProQuest Dissertations & Theses,, 2023
- 형태사항
- 1 online resource(146 p.)
- 주기사항
- Source: Dissertations Abstracts International, Volume: 84-12, Section: B.
- 주기사항
- Advisor: Wong, Wesley P. .
- 학위논문주기
- Thesis (Ph.D.)--Harvard University, 2023.
- 사용제한주기
- This item must not be sold to any third party vendors.
- 초록/해제
- 요약The thesis contains three distinct projects united by a loose theme of quantitative approaches of applying forces to molecules to answer biological questions. First, the behavior of the mechanically activated blood clotting protein von Willebrand Factor (VWF) was investigated in shear flow using both single-molecule imaging and Brownian dynamics simulations. A new method was developed, which uses patterns of light pulses to make multiple measurements of particles in flow to correct motion blur artifacts. With the experiments and simulations, our findings suggest that 1) free VWF in shear flow is not a responsive sensor for increases in shear stress, 2) the tension experienced by free VWF in physiological shear flow is lower than indicated by previous reports, and 3) that tethering to platelets or the vessel wall is required to mechanically activate VWF adhesive function for primary hemostasis. Secondly, the feasibility of using cystine-lysine distance measurements to identify proteins was evaluated based on a distance-measurement method developed in the Wong lab using optical tweezers. Finally, a high-throughput method for quantifying the strength of cell-cell interactions was developed using a modified centrifuge force microscope (CFM) with fluorescence imaging capabilities. Protein avidity can be measured at physiological densities by monitoring the unbinding of cells as a function of the applied centrifugal force. The preparation, instrument, and imaging pipeline are demonstrated by measuring an antibody-red blood cell interaction and an activated T-cell B-cell interaction.
- 일반주제명
- Biophysics.
- 일반주제명
- Biomedical engineering.
- 일반주제명
- Immunology.
- 키워드
- Blood clotting
- 키워드
- Immune cell
- 키워드
- Artifacts
- 기타저자
- Harvard University Biophysics
- 기본자료저록
- Dissertations Abstracts International. 84-12B.
- 기본자료저록
- Dissertation Abstract International
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
008240612s2023 us |||||||||||||||c||eng d■001000016932204
■00520240214100427
■006m o d
■007cr#unu||||||||
■020 ▼a9798379604530
■035 ▼a(MiAaPQ)AAI30489786
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a574.191
■1001 ▼aBergal, Hans T. .▼0(orcid)0000-0002-5499-7833
■24510▼aUsing Mechanical Force to Study Biological Processes: From Blood Clotting to Immune Cell Adhesion▼h[electronic resource]
■260 ▼a[S.l.]:▼bHarvard University. ▼c2023
■260 1▼aAnn Arbor :▼bProQuest Dissertations & Theses, ▼c2023
■300 ▼a1 online resource(146 p.)
■500 ▼aSource: Dissertations Abstracts International, Volume: 84-12, Section: B.
■500 ▼aAdvisor: Wong, Wesley P. .
■5021 ▼aThesis (Ph.D.)--Harvard University, 2023.
■506 ▼aThis item must not be sold to any third party vendors.
■520 ▼aThe thesis contains three distinct projects united by a loose theme of quantitative approaches of applying forces to molecules to answer biological questions. First, the behavior of the mechanically activated blood clotting protein von Willebrand Factor (VWF) was investigated in shear flow using both single-molecule imaging and Brownian dynamics simulations. A new method was developed, which uses patterns of light pulses to make multiple measurements of particles in flow to correct motion blur artifacts. With the experiments and simulations, our findings suggest that 1) free VWF in shear flow is not a responsive sensor for increases in shear stress, 2) the tension experienced by free VWF in physiological shear flow is lower than indicated by previous reports, and 3) that tethering to platelets or the vessel wall is required to mechanically activate VWF adhesive function for primary hemostasis. Secondly, the feasibility of using cystine-lysine distance measurements to identify proteins was evaluated based on a distance-measurement method developed in the Wong lab using optical tweezers. Finally, a high-throughput method for quantifying the strength of cell-cell interactions was developed using a modified centrifuge force microscope (CFM) with fluorescence imaging capabilities. Protein avidity can be measured at physiological densities by monitoring the unbinding of cells as a function of the applied centrifugal force. The preparation, instrument, and imaging pipeline are demonstrated by measuring an antibody-red blood cell interaction and an activated T-cell B-cell interaction.
■590 ▼aSchool code: 0084.
■650 4▼aBiophysics.
■650 4▼aBiomedical engineering.
■650 4▼aImmunology.
■653 ▼aBlood clotting
■653 ▼aImmune cell
■653 ▼aBrownian dynamics
■653 ▼aArtifacts
■653 ▼aCentrifuge force microscope
■690 ▼a0786
■690 ▼a0541
■690 ▼a0982
■71020▼aHarvard University▼bBiophysics.
■7730 ▼tDissertations Abstracts International▼g84-12B.
■773 ▼tDissertation Abstract International
■790 ▼a0084
■791 ▼aPh.D.
■792 ▼a2023
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T16932204▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
■980 ▼a202402▼f2024
