ORCID

0000-0002-1013-2619

Keywords

Actin cytoskeleton, Gelsolin, pH, Macromolecular crowding, Molybdenum disulfide, Molybdenum disulfide binding peptide 1

Subject Categories

Cell Biology | Neuroscience and Neurobiology | Other Biomedical Engineering and Bioengineering

Abstract

Actin cytoskeleton dynamics and mechanics are central to many important cellular processes, including cell morphology and motility. Gelsolin is a calcium-regulated actin binding protein involved in filament severing and filament end-capping. Intracellular environmental factors such as pH and macromolecular crowding can regulate actin cytoskeleton remodeling by gelsolin and filament mechanics. However, it is unclear how pH and macromolecular crowding can influence gelsolin-mediated filament severing activities, gelsolin-bound filament bending mechanics and conformations. The first two parts of this dissertation investigate the role of pH and macromolecular crowding on actin dynamics, filament bending stiffness and structures. To determine how intracellular environmental factors modulate gelsolin-mediated actin dynamics, mechanics and conformations, we utilized total internal reflection fluorescence microscopy, pyrene fluorescence assays, and atomic force microscopy. Biophysical analysis demonstrates that acidic pH enhances gelsolin-mediated filament severing and disassembly, and crowding increases filament length reduction by gelsolin. Further, we show that gelsolin binding increases filament flexural rigidity and shortens filament helical half-pitch. The last part of this dissertation investigates the role of molybdenum disulfide (MoS2) nanomaterial and MoS2 binding peptide 1 (MoSBP1) on actin assembly dynamics by fluorescence microscopy imaging and pyrene fluorescence assay. Nanomaterials used in various biomedical applications have been shown to influence cytoskeletal structures and cell morphogenesis. However, it is not known how the individual and combined effects of MoS2 and MoSBP1 influence actin polymerization kinetics and filament mechanics. We show that individual filament elongation and bulk assembly rates are accelerated with MoS2, while MoSBP1 alone inhibits actin assembly. Similarly, MoS2 and MoSBP1 combined reduces actin assembly kinetics. Together, these studies elucidate how gelsolin, intracellular environmental factors, and nanomaterials regulate actin dynamics and mechanics.

Completion Date

2026

Semester

Summer

Committee Chair

Kang, Ellen

Degree

Doctor of Philosophy (Ph.D.)

College

College of Sciences

Department

Physics

Format

PDF

Document Type

Dissertation

Language

English

Release Date

8-15-2028

Available for download on Tuesday, August 15, 2028

Share

COinS
 

Accessibility Statement

This item was created or digitized prior to April 24, 2027, or is a reproduction of legacy media created before that date. It is preserved in its original, unmodified state specifically for research, reference, or historical recordkeeping. In accordance with the ADA Title II Final Rule, the University Libraries provides accessible versions of archival materials upon request. To request an accommodation for this item, please submit an accessibility request form.