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Yu, Weiqun (2008) UMBRELLA CELL MECHANOTRANSDUCTION AND STRETCH-REGULATED EXOCYTOSIS/ENDOCYTOSIS. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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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.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Yu, Weiqunwey9@pitt.eduWEY9
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairApodaca, Gerardgla6@pitt.eduGLA6
Committee CoChairShroff, Sanjeev Gsshroff@pitt.eduSSHROFF
Committee MemberLin,
Committee MemberBirder, Lorilbirder@pitt.eduLBIRDER
Date: 10 June 2008
Date Type: Completion
Defense Date: 10 December 2007
Approval Date: 10 June 2008
Submission Date: 31 March 2008
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: Swanson School of Engineering > Bioengineering
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Epithelial cells; exocytosis/endocytosis; ion channels; mechanotransduction
Other ID:, etd-03312008-174958
Date Deposited: 10 Nov 2011 19:33
Last Modified: 15 Nov 2016 13:37


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