The Role of Mechanosensitive Ion Channel PIEZO1 in Detection of Confinements at Ecm
General Material Designation
[Thesis]
First Statement of Responsibility
Bahrani Fard, Mohammad Reza
Subsequent Statement of Responsibility
Hua, Susan Z.
.PUBLICATION, DISTRIBUTION, ETC
Name of Publisher, Distributor, etc.
State University of New York at Buffalo
Date of Publication, Distribution, etc.
2019
GENERAL NOTES
Text of Note
57 p.
DISSERTATION (THESIS) NOTE
Dissertation or thesis details and type of degree
M.S.
Body granting the degree
State University of New York at Buffalo
Text preceding or following the note
2019
SUMMARY OR ABSTRACT
Text of Note
Cellular response to confinement at the extracellular matrix (ECM) plays an important role during tissue development. Mishandling these mechanical signals results in a variety of diseases including cardiovascular disease and cancer. In this study, we investigate the role of mechanosensitive Piezo1 channel as a cell sensor for detection of mechanical cues at various substrates. We modified the substrates with various micropatterns, topographies, and stiffness and examined the cell shape in response to ECM modifications. By inhibiting Piezo1 activity with specific pharmacologic inhibitors or by knockout of Piezo1 with siRNA, we have shown for the first time that HEK cells lost their ability to stretch to the full extent on the stripe patterns compared with wild-type cells. This indicates that cells utilize Piezo1 channels for detection of substrate confinements. The location and concentration of Piezo1 channels were visualized using FRET-based fluorescent probes P1-cpstFRET. We show that the distribution of Piezo1 is non-uniform in cells on narrow stripes, and Piezo1 clusters exist in areas of high cytoskeletal tension. This work offers a new mechanism of mechanosensing by Piezo1 channels, through which cells utilize ECM cues for remodeling.