UMD Theses and Dissertations

Permanent URI for this collectionhttp://hdl.handle.net/1903/3

New submissions to the thesis/dissertation collections are added automatically as they are received from the Graduate School. Currently, the Graduate School deposits all theses and dissertations from a given semester after the official graduation date. This means that there may be up to a 4 month delay in the appearance of a given thesis/dissertation in DRUM.

More information is available at Theses and Dissertations at University of Maryland Libraries.

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    Simulating membrane-bound cytoskeletal dynamics
    (2023) Ni, Haoran; Papoian, Garegin A.; Biophysics (BIPH); Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    The cell membrane defines the shape of the cell and plays an indispensable role in bridging intra- and extra-cellular environments. The membrane, consisting of a lipid bilayer and various attaching proteins, mechanochemically interacts with the active cytoskeletal network that dynamically self-organizes, playing a vital role in cellular biomechanics and mechanosensing. Comprehensive simulations of membrane-cytoskeleton dynamics can bring insight in understanding how the cell mechanochemically responds to external signals, but a computational model that captures the complex cytoskeleton-membrane with both refined details and computational efficiency is lacking. To address this, we introduce in this thesis a triangulated membrane model and incorporate it with the active biological matter simulation platform MEDYAN ("Mechanochemical Dynamics of Active Networks"). This model accurately captures the membrane physical properties, showing how the membrane rigidity, the structure of actin networks and local chemical environments regulate the membrane deformations. Then, we present a new method for simulating membrane proteins, using stochastic reaction-diffusion sampling on unstructured membrane meshes. By incorporating a surface potential energy field into the reaction-diffusion sampling, we demonstrate rich membrane protein collective behaviors such as confined diffusion, liquid-liquid phase separation and membrane curvature sensing. Finally, in order to capture stretching, bending, shearing and twisting of actin filaments which are not all available with traditional actomyosin simulations, we introduce new finite-radius filament models based off Cosserat theory of elastic rods, with efficient implementation using finite-dimensional configurational spaces. Using the new filament models, we show that the filaments' torsional compliance can induce chiral symmetry breaking in a cross-linked actin bundle. All the new models are implemented in the MEDYAN platform, shedding light on whole cell simulations, paving way for a better understanding of the membrane-cytoskeleton system and its role in cellular dynamics.
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    THE ROLE OF THE ACTIN CROSSLINKER PALLADIN: FROM RECONSTITUTED NETWORKS TO LIVE CELLS
    (2013) Grooman, Brian; Upadhyaya, Arpita; Physics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Biophysics is a rapidly growing area of research. New discoveries continue to show the importance of mechanical phenomenon in biological processes, even at the cellular and sub-cellular levels. The complexity of living cells, coupled with their small size makes their study particularly difficult. Palladin is an actin-crosslinker that has not yet been studied as much as other actin-crosslinkers. It localizes with alpha-actinin in stress fibers in many adult cell types. Palladin's exact purpose is still unknown. Through in-vitro studies of reconstituted actin networks we gain insight into the mechanical importance of this novel protein, and show that when partnered with α-actinin, palladin efficiently enhances the network stiffness. Pancreatic Stellate Cells are responsible for maintaining organ integrity, and their malignant counterparts are responsible for one of the most deadly forms of cancer. Interestingly, palladin is shown to be up-regulated in tumors derived from these cells. By studying the stiffness of the cells with and without palladin (via genetic manipulation) we investigate the mechanical importance of palladin in vivo. GFP labelled palladin can serve as a useful marker because it naturally localizes into a regular pattern along stress fibers. Combined with image processing, this makes tracking local strain rates within the cell possible. Pancreatic stellate cells will respond to an applied force by actively contracting their stress fibers. The dynamics of these responses are quantified by tracking the spots of palladin. Through various pharmacological manipulations we study possible signaling pathways that lead from an applied force to stress fiber contraction. Overall, this work explores the mechanical importance of palladin and also investigates the mechanical properties of tumor-associated pancreatic stellate cells, neither of which have been previously studied. Our work shows that palladin controls network stiffness in-vitro, but not in-vivo, suggesting a yet undiscovered purpose. We have also shown that pancreatic stellate cells are in the same range of stiffness as other fibroblasts, and can actively respond to external forces. All of these findings contribute to an increased understanding of the complex systems which govern the mechanical properties of living material.