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Please use this identifier to cite or link to this item: http://arks.princeton.edu/ark:/88435/dsp01xd07gx01q
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dc.contributor.advisorHaataja, Mikko
dc.contributor.authorZhang, Ruoyao
dc.contributor.otherMechanical and Aerospace Engineering Department
dc.date.accessioned2024-04-11T20:02:02Z-
dc.date.available2024-10-07T12:00:13Z-
dc.date.created2024-01-01
dc.date.issued2024
dc.identifier.urihttp://arks.princeton.edu/ark:/88435/dsp01xd07gx01q-
dc.description.abstractMany mesoscopic membraneless organelles, also called biomolecular condensates, have shown significant biological functions in cells. Some condensates rich in proteins and nucleic acids form via liquid-liquid phase separation (LLPS), and can undergo liquid-to-solid phase transition when aging, which is related to numerous neurodegenerative diseases. In this dissertation, we develop theoretical and computational models to study phase transformations of protein-rich biomolecular condensates, focusing on the growth, coarsening, and aging behaviors. In our studies of chemically reactive macromolecular mixtures, we formulate a thermodynamic model to describe complex formation, LLPS and aging via gelation concurrently. Phase behaviors of quaternary mixtures are characterized by constructing ternary phase diagrams. We also develop a thermodynamically consistent kinetic framework to study how reaction, gelation and Brownian motion of condensates affect the coarsening and morphology of such mixtures. We find that physical cross-links in biomolecular condensates slow down the coarsening rate, while Brownian motion promotes the coarsening of gel-like domains above certain volume fraction threshold, leading to percolated structures. Aging via formation of amyloid fibrils is investigated using an integrated atomistic and continuum theory approach. We identify a new mechanism for amyloid fibrils to elongate, i.e., surface-mediated growth, different from conventional understanding. We provide quantitative analysis by constructing a continuum model that incorporates surface diffusion and attachment kinetics. There exists a critical length below which the fibril undergoes accelerated growth, and above which it reaches steady-state growth. In addition, we extend our studies to fiber growth in heterogeneous protein solutions using a phase-field modeling framework. We find that the fiber reaches a steady state characterized by its growth velocity and tip radius at different degrees of anisotropyduring the unidirectional growth in a homogeneous solution. The growth of a fiber from a protein-rich condensate to protein-poor regions results in a significant decline in growth velocity and an increase in tip radius when the fiber crosses the condensate interface. Finally, the complex and anisotropic morphologies of multiple fibers growing in a solution with multiple condensates are also illustrated. Results from this dissertation provide a better understanding of how phase transformations occur and develop in biological systems.
dc.format.mimetypeapplication/pdf
dc.language.isoen
dc.publisherPrinceton, NJ : Princeton University
dc.subjectAmyloid fibrils
dc.subjectContinuum theory
dc.subjectGelation
dc.subjectHigh-performance computing
dc.subjectLiquid-liquid phase separation
dc.subjectPhase transformation
dc.subject.classificationBiophysics
dc.subject.classificationPhysics
dc.subject.classificationBioengineering
dc.titleTheoretical and computational study of phase transformations of biomolecular condensates: growth, coarsening, and aging
dc.typeAcademic dissertations (Ph.D.)
pu.embargo.terms2024-10-05
pu.date.classyear2024
pu.departmentMechanical and Aerospace Engineering
Appears in Collections:Mechanical and Aerospace Engineering

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