자료유형  

 학위논문

Control Number  

0017163345

International Standard Book Number  

9798384023081

Dewey Decimal Classification Number  

541

Main Entry-Personal Name  

Reagle, Tyler.

Publication, Distribution, etc. (Imprint  

[S.l.] : University of Pennsylvania., 2024

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2024

Physical Description  

183 p.

General Note  

Source: Dissertations Abstracts International, Volume: 86-02, Section: B.

General Note  

Advisor: Baumgart, Tobias.

Dissertation Note  

Thesis (Ph.D.)--University of Pennsylvania, 2024.

Summary, Etc.  

요약Biomembranes are extensively inhomogeneous with respect to the compositions and distribution of the lipid molecules constructing them. The lipidome of a cell and its sub-cellular distribution constitute a nonequilibrium condition maintained by i) active expenditure of cellular energy and ii) coordination of metabolic/transport processes. Though there is lipidomic/bioinformatic evidence suggesting that the above interplay is relevant for the integration of membrane biology and lipid metabolism, the thermodynamic premises underlying a hypothesized, regulatory framework have not been rigorously tested. Moreover, the role of bilayer lipid asymmetry- referring to lipid inhomogeneity between the leaflets of a lipid bilayer- has been ignored in this context. Since bilayer lipid asymmetry is a ubiquitous feature of biomembranes across cellular life, it is likely important for membrane homeostasis, necessitating further investigation.To investigate how bilayer lipid asymmetry might serve the above role, this thesis describes observations in vesicles along with a thermodynamic analysis. These were achieved by leveraging complexation between methyl-β-cyclodextrin (mbCD) and phospholipid molecules, which adjusts the difference in the number of lipid molecules (lipid number-difference) between the leaflets of vesicles. This parameter constitutes one contribution to bilayer lipid asymmetry and mbCD-lipid complexation allowed its effects upon i) vesicle morphology, ii) bilayer phase behavior, and iii) lipid thermodynamics to be investigated. Evidence suggests that lipid number-difference modulates the chemical potential (and activity) of lipids within a bilayer.Then, to investigate generation of lipid number-difference by a transmembrane protein, an active phospholipid transporter (a flippase) of the ATP-binding cassette transporter superfamily was purified and reconstituted into a bilayer environment. This was done to eventually investigate the i) conformation and ii) catalytic efficiency of flippases in this superfamily with respect to lipid number-difference (by leveraging mbCD-lipid chemistry). Challenges encountered during purification/reconstitution are described and recommended actions proposed. Achievement of the aims associated with these efforts could contextualize i) the allosteric regulation and ii) energy transduction of such proteins within a control scheme for maintenance of membrane homeostasis.

Subject Added Entry-Topical Term  

Physical chemistry.

Subject Added Entry-Topical Term  

Biochemistry.

Subject Added Entry-Topical Term  

Biophysics.

Index Term-Uncontrolled  

Chemical equilibrium

Index Term-Uncontrolled  

Lipid membranes

Index Term-Uncontrolled  

Membrane asymmetry

Index Term-Uncontrolled  

Membrane morphology

Index Term-Uncontrolled  

Methyl-beta-cyclodextrin

Added Entry-Corporate Name  

University of Pennsylvania Chemistry

Host Item Entry  

Dissertations Abstracts International. 86-02B.

Electronic Location and Access  

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Control Number  

joongbu:656074