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Research Spending & Results

Award Detail

Doing Business As Name:University of Utah
  • Tamara C Bidone
  • (617) 945-3966
  • Martin A Schwartz
Award Date:12/29/2020
Estimated Total Award Amount: $ 396,319
Funds Obligated to Date: $ 396,319
  • FY 2021=$396,319
Start Date:04/01/2021
End Date:03/31/2024
Transaction Type:Grant
Awarding Agency Code:4900
Funding Agency Code:4900
CFDA Number:47.041
Primary Program Source:040100 NSF RESEARCH & RELATED ACTIVIT
Award Title or Description:Regulation of Cell Adhesions by Mechanical Force
Federal Award ID Number:2044394
DUNS ID:009095365
Parent DUNS ID:009095365
Program:BMMB-Biomech & Mechanobiology
Program Officer:
  • Laurel Kuxhaus
  • (703) 292-4465

Awardee Location

Street:75 S 2000 E
County:Salt Lake City
Awardee Cong. District:02

Primary Place of Performance

Organization Name:University of Utah
Street:72 South Central Campus Drive
City:Salt Lake City
County:Salt Lake City
Cong. District:02

Abstract at Time of Award

This project aims to understanding how biological materials respond to mechanical force. Adhesion receptors are proteins in the plasma membrane that mediate cell binding to other cells or to the extracellular matrix. These receptors sense and transmit forces between cells and the external environment. Specifically, integrins transmit mechanical and biochemical information. This information critically guides life processes such as embryonic development, and also plays a role in diseases such as cancer, hypertension, osteoporosis and atherosclerosis. Integrins undergo drastic, long-range changes in response to biochemical signals or mechanical stresses. Exactly how integrin amino acid residues rearrange in response to force is largely unknown due to the technical challenges in observing shifts in residue positions and interactions at the single protein level. This hampers our ability to understand or modulate these processes that can lead to disease. This research will employ cell biology, computational simulations, biophysics, chemistry and material science approaches to elucidate the detailed pathways of force-dependent changes in integrins conformation and their roles in cell regulation. The overarching objective of this research is to understand, at near-atomic level, how integrin conformation is modulated by mechanical force and how the resultant conformational transitions regulate cell behavior. The research team will develop new numerical tools to perform molecular dynamics simulations of integrins under force. These models will be used to predict mutations that stabilize or destabilize specific integrin states, which will then be tested experimentally for their effects on mechanosensing in live cells. By combining modeling with experiments, we will elucidate detailed pathways of force-dependent conformational transitions and their role in biology. This multidisciplinary approach will broaden the participation of diverse communities and underrepresented groups and positively impact engineering and material science education. Furthermore, this research may result in new approaches to design and produce biomimetic and smart materials for engineering applications. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

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