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).

Public Health Relevance

Our Resource develops new instrument technologies for enabling flexible force measurements. Including magnetic technologies, integrated atomic force and fluorescence microscopy, and development of software to control magnetic fields and tracking. We continue to bring cutting-edge devices, techniques, and research in computer science to bear on biomedical research, design and implement techniques to display models and real-time simulations aligned in space and time with experimental results.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Biotechnology Resource Grants (P41)
Project #
5P41EB002025-30
Application #
8601184
Study Section
Special Emphasis Panel (ZRG1-CB-D (40))
Program Officer
Hunziker, Rosemarie
Project Start
1984-05-01
Project End
2014-12-31
Budget Start
2014-01-01
Budget End
2014-12-31
Support Year
30
Fiscal Year
2014
Total Cost
$851,469
Indirect Cost
$269,952
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
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Burridge, Keith; Guilluy, Christophe (2016) Focal adhesions, stress fibers and mechanical tension. Exp Cell Res 343:14-20
Blackmon, Richard L; Sandhu, Rupninder; Chapman, Brian S et al. (2016) Imaging Extracellular Matrix Remodeling In Vitro by Diffusion-Sensitive Optical Coherence Tomography. Biophys J 110:1858-68
Wang, Hui; Hahn, Klaus M (2016) LOVTRAP: A Versatile Method to Control Protein Function with Light. Curr Protoc Cell Biol 73:21.10.1-21.10.14
Lawrimore, Josh; Aicher, Joseph K; Hahn, Patrick et al. (2016) ChromoShake: a chromosome dynamics simulator reveals that chromatin loops stiffen centromeric chromatin. Mol Biol Cell 27:153-66
Gentry, Leanna R; Karginov, Andrei V; Hahn, Klaus M et al. (2016) Characterization of an Engineered Src Kinase to Study Src Signaling and Biology. Methods Mol Biol 1360:157-67
Cribb, Jeremy A; Osborne, Lukas D; Beicker, Kellie et al. (2016) An Automated High-throughput Array Microscope for Cancer Cell Mechanics. Sci Rep 6:27371

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