Browsing by Subject "Membrane permeability"

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    Exploring the Role of the Cell Membrane in Formaldehyde Stress Tolerance in Methylorubrum extorquens
    (2024-01) Singla, Deepanshu
    Methanol is a promising alternative to sugars as a feedstock for bacteria in biomanufacturing as it does not compete with food demands and can be sustainably produced from greenhouse gases. Methylorubrum extorquens is a methylotroph that naturally uses reduced single-carbon compounds, such as methanol, as a sole source of carbon and energy. Understanding the metabolic regulation and physiology of M. extorquens will enable the adoption of methanol in the fermentation industry. Methanol utilization flows through formaldehyde, a toxic intermediate, which is generated in the periplasm and then moves into the cytoplasm to be further metabolized. However, the regulation of formaldehyde movement across inner cell membrane has not been studied in M. extorquens. Formaldehyde can damage proteins and DNA by forming diverse crosslinks or diffuse into lipid membranes and react with unsaturated bonds, damaging lipids and potentially disrupting the membrane. As most fatty acids in M. extorquens lipidome are unsaturated, we suspect they are prone to damage and that M. extorquens must have strategies for mitigating this damage. Here we show that cells acclimated to exogenous or endogenous formaldehyde have reduced membrane permeability and an altered lipid profile. We hypothesize that reduced membrane permeability limits the formaldehyde diffusion through membrane, regulating formaldehyde flux and preventing contact with unsaturated fatty acids which may make the membranes more resistant to formaldehyde mediated damage.
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    Nanoclay Crosslinked pH-Sensitive Hydrogel for Rhythmic Hormone Delivery
    (2019-10) Hu, Xueyao
    Gonadotropin releasing hormone (GnRH) is secreted in rhythmic pulses every 1–2 hours. Disruption of this pulsatile release is associated with pathologies in reproductive function and sexual development. In order to approach an implantable, rhythmic delivery system for GnRH, a published prototype has been demonstrated that can generate rhythmic pulses of GnRH release in response to a constant glucose level. In this thesis, the prototype was altered with the intent to advance the development of a practical, implantable system. First, the commercial pH stat was replaced by a self-assembled one. The customized pH-stat was suitable for most titration conditions. Second, the durability of the membrane used in the system was improved. Third, the ratio of the membrane surface to the volume of delivery system was increased to speed up the systems oscillatory behavior. While these modifications improved the practicality of the delivery system, it resulted in the lose of pulsatile release behavior, for unknown reasons. A systematic approach is suggested, which can reveal the root cause analysis of the failure.