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 #
5P41EB002025-29
Application #
8422870
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
2013-01-01
Budget End
2013-12-31
Support Year
29
Fiscal Year
2013
Total Cost
$940,704
Indirect Cost
$291,126
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
Lessey-Morillon, Elizabeth C; Osborne, Lukas D; Monaghan-Benson, Elizabeth et al. (2014) The RhoA guanine nucleotide exchange factor, LARG, mediates ICAM-1-dependent mechanotransduction in endothelial cells to stimulate transendothelial migration. J Immunol 192:3390-8
Guilluy, Christophe; Osborne, Lukas D; Van Landeghem, Laurianne et al. (2014) Isolated nuclei adapt to force and reveal a mechanotransduction pathway in the nucleus. Nat Cell Biol 16:376-81
Fisher, J K; Kleckner, N (2014) Magnetic force micropiston: an integrated force/microfluidic device for the application of compressive forces in a confined environment. Rev Sci Instrum 85:023704
Cao, Tian; Zach, Christopher; Modla, Shannon et al. (2014) Multi-modal registration for correlative microscopy using image analogies. Med Image Anal 18:914-26
Hong, Yi; Gao, Yi; Niethammer, Marc et al. (2014) Depth-based shape-analysis. Med Image Comput Comput Assist Interv 17:17-24
Mair, L O; Superfine, R (2014) Single particle tracking reveals biphasic transport during nanorod magnetophoresis through extracellular matrix. Soft Matter 10:4118-25
Taylor 2nd, Russell M; Harter, Jonathan (2014) Random per-element luminance modulation for improved visual tracking. IEEE Comput Graph Appl 34:83-7
Hong, Yi; Singh, Nikhil; Kwitt, Roland et al. (2014) Time-warped geodesic regression. Med Image Comput Comput Assist Interv 17:105-12
Hong, Yi; Davis, Brad; Marron, J S et al. (2014) Statistical atlas construction via weighted functional boxplots. Med Image Anal 18:684-98
Collins, Caitlin; Osborne, Lukas D; Guilluy, Christophe et al. (2014) Haemodynamic and extracellular matrix cues regulate the mechanical phenotype and stiffness of aortic endothelial cells. Nat Commun 5:3984

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