Researcher ORCID Identifier
0000-0001-5203-4825
Graduation Year
2025
Document Type
Open Access Senior Thesis
Degree Name
Bachelor of Arts
Department
Molecular Biology
Second Department
Chemistry
Reader 1
Malkiat S. Johal
Reader 2
Matthew H. Sazinsky
Terms of Use & License Information
This work is licensed under a Creative Commons Attribution 4.0 License.
Rights Information
© 2025 Ethan M. Fong
Abstract
Statins interact with lipid membranes in ways that shape their pharmacokinetics, off-target effects, and pleiotropic actions, yet these interactions' mechanical and biophysical consequences remain poorly understood. This thesis employs a combination of surface plasmon resonance (SPR), quartz crystal microbalance with dissipation monitoring (QCM-D), and rheological modelling to characterize how representative statins intercalate within biomimetic supported lipid bilayers (SLBs) of healthy and diseased composition. SPR reveals that lipophilic statins exhibit higher apparent affinities and slower dissociation kinetics, especially in cholesterol- and anionic lipid-rich membranes. QCM-D analyses demonstrate that statins alter membrane mass, dissipation, and interfacial stiffness in a statin- and membrane-dependent manner. Frequency sweeps of the storage modulus (G′) reveal nonlinear elastic remodelling after statin loading, with Zener model fits yielding nanosecond-scale relaxation times that shorten in both membrane types, indicative of membrane fluidization. Notably, healthy SLBs exhibit mechanical hysteresis and dissipative remodelling that fails to reverse after Pravastatin washout, while diseased SLBs undergo reversible elastic softening. Mapping frequency–dissipation trajectories further reveals asymmetric mechanical pathways between membrane types. Together, these results demonstrate that statin–membrane interactions are both composition-dependent and mechanically consequential, explaining tissue-specific statin effects mechanistically. This work supports a biomechanical theory of statin selectivity, wherein membrane composition governs drug partitioning and the mechanical remodelling that determines statin retention, efficacy, and cytotoxic potential in healthy versus diseased cellular environments.
Recommended Citation
Fong, Ethan M., "BIOMECHANICS OF THE ATHEROSCLEROTIC LIPIDOME: (UN)EXPECTED STATIN INTERACTIONS AND MEMBRANE REMODELLING" (2025). Pomona Senior Theses. 359.
https://scholarship.claremont.edu/pomona_theses/359
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