The long-term goal of this project is to understand how physical signals complement chemical signals for modulating cellular functions and interactions with the environment. Adherent cells generate mechanical forces to propel migration and drive environment remodeling. They also use mechanical forces to probe the environment, sense their own physical state, communicate with neighboring cells, and possibly coordinate functions within the cell. Previous studies suggested that these physical interactions regulate cell growth, differentiation, and migration, and affect a broad range of health-related issues such as tissue repair and cancer. This project will apply a combination of materials, microfabrication, micromanipulation, microfluidic, and computational approaches to understand mechanical activities and their regulation at the front and rear of a migrating cell.
The first aimi s designed to determine how the front end of a cell detects surface rigidity and how cellular mechanical output is regulated in relation to the state of migration.
The second aim i s designed to determine how the rear end of a cell is positioned, and how microtubules, centrosomes, and intracellular tension may regulate the process. Information from this project will have a broad impact on human health, particularly tissue regeneration, embryogenesis, and cancer treatment.

Public Health Relevance

This project will apply multidisciplinary approaches to seek fundamental understanding of the mechanics of cell migration, including the generation of mechanical forces and the responses to external mechanical signals. The research will elucidate how cells propel and guide their migration, how they detect their own state of migration for regulating internal activities, and how they coordinate events at the tip and tail. Given the broad involvement of cell migration in physiological and pathological processes from tissue regeneration to metastatic invasion, results of this project are expected to impact on a wide range of clinical treatments.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM118998-03
Application #
9538217
Study Section
Nuclear and Cytoplasmic Structure/Function and Dynamics Study Section (NCSD)
Program Officer
Deatherage, James F
Project Start
2016-09-28
Project End
2020-07-31
Budget Start
2018-08-01
Budget End
2019-07-31
Support Year
3
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Carnegie-Mellon University
Department
Biomedical Engineering
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
052184116
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Li, David; Wang, Yu-Li (2018) Coordination of cell migration mediated by site-dependent cell-cell contact. Proc Natl Acad Sci U S A 115:10678-10683
Zhang, Jian; Wang, Yu-Li (2017) Centrosome defines the rear of cells during mesenchymal migration. Mol Biol Cell 28:3240-3251