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Phase Equilibria and Dynamics of Intrinsically Disordered Proteins in Biological Condensates
Phase Equilibria and Dynamics of Intrinsically Disordered Proteins in Biological Condensates
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20250211152840
- ISBN
- 9798346759331
- DDC
- 574.191
- 저자명
- Rana, Ushnish.
- 서명/저자
- Phase Equilibria and Dynamics of Intrinsically Disordered Proteins in Biological Condensates
- 발행사항
- [Sl] : Princeton University, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 111 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 86-06, Section: B.
- 주기사항
- Advisor: Panagiotopoulos, Athanassios Z.;Brangwynne, Clifford P.
- 학위논문주기
- Thesis (Ph.D.)--Princeton University, 2024.
- 초록/해제
- 요약Biomolecular condensates, which are phase separated assemblies of proteins and nucleic acids, have emerged as a new paradigm behind the spatiotemporal organization of the cellular interior. Understanding the biophysical principles driving the phase behavior of these biomolecules is of fundamental importance for deciphering the biological function of these structures.It has been well established that the phase behavior of biological condensates is highly sensitive to the sequence of the phase separation capable proteins. However, there are still open questions regarding how sequence specificity drives condensation. In this work, I first addressed how protein sequence can drive the phase equilibria of condensates towards aggregation instead of phase separation. Utilizing a simple lattice model of disordered proteins alongside Grand Canonical Monte Carlo simulations, we establish an approximate order parameter that distinguishes whether a protein sequence phase separates or aggregates. Building on our knowledge of sequence order parameters, I then address how both protein sequence and oligomerization together influence the behavior of multicomponent multiphasic condensates. Our results show that large sequence differences between disordered proteins are required for driving the formation of multiple demixed phases, suggesting that other mechanisms might be at play behind the formation of endogenous multiphasic condensates. Instead, differential oligomerization of disordered proteins can cause demixing and formation of multiphasic condensates. Furthermore, I validate our simulations by performing in vivo reconstitution experiments. Our results highlight how asymmetric oligomerization and sequence patterning underlie the formation of multiphasic condensates. I expect these results to be of potential significance for the design of de novo condensates for synthetic biology. Given the interest in developing new engineered condensates for metabolic engineering, I also investigated how condensate composition and interaction architecture influence exchange across their interfaces. I find that increasing affinity be-tween a protein scaffold and its client molecules causes interfacial exchange to slow down substantially beyond a threshold interaction strength.Taken together, the findings presented in this dissertation further our understanding of the biophysical principles behind the formation of biological condensates. These results would enable future studies that aim to engineer for synthetic biology applications as well as those aimed at drugging endogenous condensates for therapeutic applications.
- 일반주제명
- Biophysics
- 일반주제명
- Chemical engineering
- 일반주제명
- Bioengineering
- 키워드
- Phase equilibria
- 기타저자
- Princeton University Chemical and Biological Engineering
- 기본자료저록
- Dissertations Abstracts International. 86-06B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■020 ▼a9798346759331
■035 ▼a(MiAaPQ)AAI31562604
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a574.191
■1001 ▼aRana, Ushnish.▼0(orcid)0000-0001-6783-6193
■24510▼aPhase Equilibria and Dynamics of Intrinsically Disordered Proteins in Biological Condensates
■260 ▼a[Sl]▼bPrinceton University▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a111 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 86-06, Section: B.
■500 ▼aAdvisor: Panagiotopoulos, Athanassios Z.;Brangwynne, Clifford P.
■5021 ▼aThesis (Ph.D.)--Princeton University, 2024.
■520 ▼aBiomolecular condensates, which are phase separated assemblies of proteins and nucleic acids, have emerged as a new paradigm behind the spatiotemporal organization of the cellular interior. Understanding the biophysical principles driving the phase behavior of these biomolecules is of fundamental importance for deciphering the biological function of these structures.It has been well established that the phase behavior of biological condensates is highly sensitive to the sequence of the phase separation capable proteins. However, there are still open questions regarding how sequence specificity drives condensation. In this work, I first addressed how protein sequence can drive the phase equilibria of condensates towards aggregation instead of phase separation. Utilizing a simple lattice model of disordered proteins alongside Grand Canonical Monte Carlo simulations, we establish an approximate order parameter that distinguishes whether a protein sequence phase separates or aggregates. Building on our knowledge of sequence order parameters, I then address how both protein sequence and oligomerization together influence the behavior of multicomponent multiphasic condensates. Our results show that large sequence differences between disordered proteins are required for driving the formation of multiple demixed phases, suggesting that other mechanisms might be at play behind the formation of endogenous multiphasic condensates. Instead, differential oligomerization of disordered proteins can cause demixing and formation of multiphasic condensates. Furthermore, I validate our simulations by performing in vivo reconstitution experiments. Our results highlight how asymmetric oligomerization and sequence patterning underlie the formation of multiphasic condensates. I expect these results to be of potential significance for the design of de novo condensates for synthetic biology. Given the interest in developing new engineered condensates for metabolic engineering, I also investigated how condensate composition and interaction architecture influence exchange across their interfaces. I find that increasing affinity be-tween a protein scaffold and its client molecules causes interfacial exchange to slow down substantially beyond a threshold interaction strength.Taken together, the findings presented in this dissertation further our understanding of the biophysical principles behind the formation of biological condensates. These results would enable future studies that aim to engineer for synthetic biology applications as well as those aimed at drugging endogenous condensates for therapeutic applications.
■590 ▼aSchool code: 0181.
■650 4▼aBiophysics
■650 4▼aChemical engineering
■650 4▼aBioengineering
■653 ▼aPhase equilibria
■653 ▼aBiomolecular condensates
■653 ▼aDisordered proteins
■653 ▼aBiological condensates
■690 ▼a0786
■690 ▼a0542
■690 ▼a0202
■71020▼aPrinceton University▼bChemical and Biological Engineering.
■7730 ▼tDissertations Abstracts International▼g86-06B.
■790 ▼a0181
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17164179▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
