A cell's mechanical microenvironment an influence its behavior, from its adhesive and cytoskeletal structure to the genes it expresses, and has been shown to affect complex biological processes such as stem cell differentiation and tumor progression. However, the manner in which a cell measures and interprets mechanical information in its microenvironment, particularly transient mechanical signals such as those experienced during development and wounding, is unclear. The proposed work will explore these questions by directly imaging the accumulation of mRNA transcripts and transcription factor localization in live cells as the mechanical microenvironment is altered using force microscopy. In this way, we will be able to decipher the thresholds of mechanical stimuli, include stiffness changes or force changes, and the patterns of mechanical inputs, including continuous, oscillatory, and pulsed stimuli, that can elicit a genetic response, and vary the patterns of mechanical inputs to determine how a cell integrates transient short-timescale mechanical inputs into sustained long-timescale genetic responses, moving us toward a detailed mechanism for mechanosensitive gene regulation.

Public Health Relevance

Tumor progression and stem cell differentiation are cellular processes that are affected by the mechanical microenvironment a cell finds itself in, though how a cell senses and interprets mechanical information in its microenvironment is not well understood. The proposed work will advance our knowledge of this sensing process, identifying key parts that could serve as targets for drug therapies and informing how to design engineered tissues for regenerative therapies.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32GM101911-01
Application #
8317223
Study Section
Special Emphasis Panel (ZRG1-F05-P (20))
Program Officer
Sakalian, Michael
Project Start
2012-07-01
Project End
2014-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
1
Fiscal Year
2012
Total Cost
$49,214
Indirect Cost
Name
University of California Berkeley
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94704
Ricca, Benjamin L; Venugopalan, Gautham; Fletcher, Daniel A (2013) To pull or be pulled: parsing the multiple modes of mechanotransduction. Curr Opin Cell Biol 25:558-64