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Gastric mucin and Helicobacter pylori: Rheology, microrheology and microscopy studies

Posted on:2008-11-09Degree:Ph.DType:Dissertation
University:Boston UniversityCandidate:Celli, Jonathan PaulFull Text:PDF
GTID:1444390005465505Subject:Biology
Abstract/Summary:
This dissertation examines the relationship between the viscoelastic properties of gastric mucin, a high molecular weight glycoprotein responsible for the gel-forming property of the protective gastric mucus layer, and Helicobacter pylori (H. pylori), the ulcer causing bacterium which is able to colonize the human stomach by elevating the pH of its environment. Insights presented here into the mechanism by which H. pylori alters, and is able to swim through the protective mucus layer may enhance our understanding of ulcer physiology and ultimately influence protocols for treatment of this and other diseases caused by this bacteria.; Bulk rheology experiments demonstrate that gastric mucin undergoes a pH-dependent sol-gel transition characterized by reversal from loss dominated response (G'(o) < G"(o)) to storage dominated response (G'(o) < G"(o)) as pH is lowered, going through a critical gel transition near pH 4. Mucin gels are also found to fail dramatically above a yield stress of ∼10 Pascal and exhibit dramatic shear thinning behavior. In the presence of H. pylori a profound loss of mucin viscoelasticity appears to be directly correlated with the elevation in pH caused by the bacteria.; Particle tracking microrheology studies examining the thermal motion of probe particles provide further evidence of the pH-dependent sol-gel transition and also probe the local heterogeneous structure of mucin gels. In other microrheology experiments using a microscope based dynamic light scattering instrument, it is observed that small tracer particles actually have higher local mobility in the low pH mucin gel in which relatively large water filled pores open up, than in the solution state in which their diffusion is more uniformly hampered.; Microscopy studies examining the motility of H. pylori through gastric mucin show that while able to swim freely at neutral pH, the bacteria are entangled in the gel at low pH and unable to translate. Analysis of the dynamics of a stuck bacterium provides unique insight into the poorly understood problem of motility in a viscoelastic environment. In the presence of urea the bacterium elevates the pH of its surroundings, triggering the transition from gel to sol and enabling it to swim freely.
Keywords/Search Tags:Gastric mucin, Pylori, Microrheology, Transition, Gel
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