The hallmarks of like - motility, adaptation and replication - occur because molecules as Individuals and organized into cells and tissues, generate and respond to forces. The coordinated activity of thousands of molecular motors within single cells oscillates cilia to cause the flow of the pulmonary barrier fluid over long distances. Infection, Inflammation, and metastasis involve the motility of single cells moving through internal changes of shape with forces pushing against their own membranes, peeling, pulling, and rolling with specific proteins in the lumen of blood vessels, or propelled by polymerization of molecular units. Replication involves the wholesale rearrangement of chromosomes through the mitotic spindle, generating forces to organize the chromosomes along the midplate, sensing forces to pass through the checkpoint to finally pull the kinetochores poleward with polymerization forces. Over the past decade the advances in structure identification through genomics and proteomics has been matched by exquisite tools for understanding function through forces. The goal of our resource is to develop force technologies to be applied over a wide range of biological settings, from the single molecule to the tissue level, with integrated systems that orchestrate facile control, multimodal imaging and analysis through visualization and modeling. The individual collaboration projects that steer our technology development cover a wide range of phenomena in molecular biophysics, cell biology and biomedical science. They cover length scales ranging from single molecule (mucin, myosin, MutS) to macromolecular complexes (fibrin fibers, viruses), cells (Plexin, cell motility, cell division), tissue cultures (human lung cell cultures) and macroscopic biomaterial properties (mucus rheology).

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Biotechnology Resource Grants (P41)
Project #
5P41EB002025-27
Application #
8032509
Study Section
Special Emphasis Panel (ZRG1-CB-D (40))
Program Officer
Zullo, Steven J
Project Start
1984-05-01
Project End
2014-12-31
Budget Start
2011-01-01
Budget End
2011-12-31
Support Year
27
Fiscal Year
2011
Total Cost
$1,184,538
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Physics
Type
Schools of Arts and Sciences
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Boulter, Etienne; Estrach, Soline; Tissot, Floriane S et al. (2018) Cell metabolism regulates integrin mechanosensing via an SLC3A2-dependent sphingolipid biosynthesis pathway. Nat Commun 9:4862
Beicker, Kellie; O'Brien 3rd, E Timothy; Falvo, Michael R et al. (2018) Vertical Light Sheet Enhanced Side-View Imaging for AFM Cell Mechanics Studies. Sci Rep 8:1504
van Haren, Jeffrey; Charafeddine, Rabab A; Ettinger, Andreas et al. (2018) Local control of intracellular microtubule dynamics by EB1 photodissociation. Nat Cell Biol 20:252-261
Stefanini, Lucia; Lee, Robert H; Paul, David S et al. (2018) Functional redundancy between RAP1 isoforms in murine platelet production and function. Blood 132:1951-1962
Yumerefendi, Hayretin; Wang, Hui; Dickinson, Daniel J et al. (2018) Light-Dependent Cytoplasmic Recruitment Enhances the Dynamic Range of a Nuclear Import Photoswitch. Chembiochem 19:1319-1325
Ma, Xiao; Dagliyan, Onur; Hahn, Klaus M et al. (2018) Profiling cellular morphodynamics by spatiotemporal spectrum decomposition. PLoS Comput Biol 14:e1006321
Yan, Connie; Wang, Fei; Peng, Yun et al. (2018) Microtubule Acetylation Is Required for Mechanosensation in Drosophila. Cell Rep 25:1051-1065.e6
Dagliyan, Onur; Krokhotin, Andrey; Ozkan-Dagliyan, Irem et al. (2018) Computational design of chemogenetic and optogenetic split proteins. Nat Commun 9:4042
Takano, Tetsuya; Wu, Mengya; Nakamuta, Shinichi et al. (2017) Discovery of long-range inhibitory signaling to ensure single axon formation. Nat Commun 8:33
Bays, Jennifer L; Campbell, Hannah K; Heidema, Christy et al. (2017) Linking E-cadherin mechanotransduction to cell metabolism through force-mediated activation of AMPK. Nat Cell Biol 19:724-731

Showing the most recent 10 out of 163 publications