Cells interact with mechanical environments by mechanotransduction, a cellular process that converts mechanical signals into biochemical signals. Umbrella cells respond to mechanical stimuli by increasing exocytosis, endocytosis, and ion transport, but how these processes are coordinated and the mechanotransduction pathways involved are not well understood. By manipulating different forces and force parameters applied on umbrella cells, the responses of electrophysiological parameters (TEV, TER, and Isc) and apical membrane capacitance (1µF 1cm2 membrane surface area) are monitored through the modified Ussing chamber system. Stretch of the umbrella cells result in an acute change of electrical parameters, but not hydrostatic pressure. Further, the stretched response is sensitive to force direction, indicating that stretch of apical membrane causes umbrella cell TEV hyperpolarization, TER decrease, Isc increase, and apical membrane exocytosis, while stretch of basolateral membrane causes opposite effects, and this observation can be modeled mathematically. Stretch speed, which is defined by the filling rate, is further defined to play the key role in modulating the degree and time course of stretched umbrella cell responses, suggesting a mechnosensory function of umbrella cells. Use of channel blockers and openers established that the stretch of apical membrane is likely dependent on cation transport pathway, while stretch of basolateral membrane is dependent on K+ transport at the basolateral surface of the cells, indicating distinctive apical and basolateral membrane requirements for umbrella cell mechanotransduction. These results indicate that mechanotransduction in umbrella cells depends on the sequential activity of its distinct apical and basolateral membrane domains, which act in a collaborative manner to regulate apical membrane dynamics.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-03312008-174958 |
| Date | 10 June 2008 |
| Creators | Yu, Weiqun |
| Contributors | Gerard Apodaca, Lori Birder, Sanjeev G. Shroff, Hai Lin |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-03312008-174958/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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