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Uncovering Structure-Property Relations in Biomimetic Lipid Membranes with Molecular AdditivesLihiniya Kumarage, Teshani Omanthika 15 August 2024 (has links)
The lipid bilayer, the fundamental structure of cell membranes, exemplifies a highly adaptable molecular assembly with characteristics that have been fine-tuned through evolution to meet the diverse functional needs of cells. These bilayers must strike a delicate balance: they need to be sufficiently rigid to act as protective barriers, yet fluid enough to facilitate the diffusion of proteins and molecular clusters crucial for various biological processes. Owing to their multifunctional nature, lipid membranes are not only vital in biological contexts but also in numerous practical applications, such as artificial cells, drug-delivery nanocarriers, and biosensors. Both biological and synthetic lipid membranes frequently incorporate molecular or nanoscale additives that modify their properties through a range of mechanisms. Gaining a comprehensive understanding of how lipid membranes interact with these additives is an area of active research, particularly with the advent of advanced high-resolution characterization techniques that reveal both the static and dynamic behaviors of these systems.
This dissertation investigates the impact of small molecular additives – specifically natural and synthetic sterols – on the structure, elasticity, and organization of biomimetic lipid membranes. Utilizing advanced scattering techniques and other methods, the research elucidates the intricate interplay between the membrane composition, structure, and elasticity. Key findings demonstrate that, unlike previous observations, cholesterol significantly affects the bending rigidity of lipid membranes regardless of chain unsaturation, when measured on mesoscopic length and time scales. Interestingly, the replacement of cholesterol with engineered molecules, comprised of a sterol unit that is chemically conjugated to one or both of the lipid chains, results in further enhancement in the membrane bending rigidity and mechanical stability, making them a promising additive for advanced liposomal drug delivery systems. Further studies on phase-separating membranes illustrate the effective use of sterol-modified lipids in regulating the formation and size of distinct lipid domains implicated in protein recruitment and biological function. This work advances the current understanding of membrane biophysics and paves the way for novel therapeutic strategies and biomaterial designs. / Doctor of Philosophy / Cells are the central unit of life found in all living organisms. The outermost layer of the cell, the plasma membrane, is quite complex. Yet it is primarily formed by the self-assembly of lipids and sterols that form a bilayer structure that mediates important biological functions. To understand the properties of plasma cell membranes and their implication in function, biophysicists use model cell membranes to reduce biological complexity. This dissertation explores changes in the structure and dynamics of model lipid membranes in response to small molecular additives, including cholesterol and hybrid cholesterol analogues. Using sophisticated scientific techniques, experiments reveal that cholesterol stiffens lipid membranes, regardless of the architecture of their molecular building blocks. These findings challenge previous beliefs and suggest a universal rule for membrane stiffness with cholesterol. What is more, synthetic additives formed by conjugating lipid and cholesterol structures are even better than cholesterol at stabilizing membranes. This discovery has practical implications for improving drug delivery systems. Additional studies provide new insights into how additives can control how lipids organize into distinct domains that are important for many biological processes. Overall, this work enhances our understanding of cell membranes and opens up new possibilities for developing advanced medical treatments and tunable biomaterials.
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Lateral torsional buckling of rectangular reinforced concrete beamsKalkan, Ilker 10 November 2009 (has links)
The study presents the results of an experimental and analytical investigation aimed at examining the lateral stability of rectangular reinforced concrete slender beams. In the experimental part of the investigation, a total of eleven reinforced concrete beams having a depth to width ratio between 10.20 and 12.45 and a length to width ratio between 96 and 156 were tested. Beam thickness, depth and unbraced length were 1.5 to 3.0 in., 18 to 44 in., and 12 to 39.75 ft, respectively. Each beam was subjected to a single concentrated load applied at midspan by means of a gravity load simulator that allowed the load to always remain vertical when the section displaces out of plane. The loading mechanism minimized the lateral translational and rotational restraints at the load application point to simulate the nature of gravity load. Each beam was simply-supported in and out of plane at the ends. The supports allowed warping deformations, yet prevented twisting rotations at the beam ends.
In the analytical part of the study, a formula was developed for determining the critical loads of lateral torsional buckling of rectangular reinforced concrete beams free from initial geometric imperfections. The influences of shrinkage cracking and inelastic stress-strain properties of concrete and the contribution of longitudinal reinforcement to the lateral stability are accounted for in the critical load formula. The experiments showed that the limit load of a concrete beam with initial geometric imperfections can be significantly lower than the critical load corresponding to its geometrically perfect configuration. Accordingly, a second formula was developed for the estimation of limit loads of reinforced concrete beams with initial lateral imperfections, by introducing the destabilizing effect of sweep to the critical load formula.
The experimental results were compared to the proposed analytical solution and to various lateral torsional buckling solutions in the literature. The formulation proposed in the present study was found to agree well with the experimental results. The incorporation of the geometric and material nonlinearities into the formula makes the proposed solution superior to the previous lateral torsional buckling solutions for rectangular reinforced concrete beams.
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