This project aims at causing a major paradigm-shift in regenerative medicine. In the past, attempts to re-establish synaptic connectivity following injury have met great difficulties. A new work yielded evidence that mechanical force, applied either naturally or artificially at individual nascent synapses, initiates and enhances their connectivity. This FORCE (force orchestrated retrograde synaptic enhancement) mechanism is likely based on a property of cells conserved through evolution and, thus, has the potential to apply widely including regenerative medicine. In this project, we seek to establish the basis for novel strategies that make synaptic restoration possible. Genetics, bioengineering, computational bioinformatics and nanotechnology will be combined to test the hypothesis: mechanical force not only initiates and enhances but also restores neural connectivity. If successful, this project will shift the focus in regenerative medicine from moleculo-centric to mechano-centric approaches.

Public Health Relevance

This project aims to introduce an important new concept to regenerative neuromedicine. Regeneration of central nervous system neurons after injury faces daunting challenges. We propose to explore the potential of mechanical force being an integral part of initiation, enhancement and restoration of synapses in vivo and, thereby, seek to establish a foundation for novel neural restoration strategies. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS063405-01
Application #
7515857
Study Section
Special Emphasis Panel (ZNS1-SRB-P (44))
Program Officer
Talley, Edmund M
Project Start
2008-08-01
Project End
2012-07-31
Budget Start
2008-08-01
Budget End
2009-07-31
Support Year
1
Fiscal Year
2008
Total Cost
$297,749
Indirect Cost
Name
University of Miami Coral Gables
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
625174149
City
Coral Gables
State
FL
Country
United States
Zip Code
33146
Fan, Anthony; Tofangchi, Alireza; Kandel, Mikhail et al. (2017) Coupled circumferential and axial tension driven by actin and myosin influences in vivo axon diameter. Sci Rep 7:14188
Tofangchi, Alireza; Fan, Anthony; Saif, M Taher A (2016) Mechanism of Axonal Contractility in Embryonic Drosophila Motor Neurons In Vivo. Biophys J 111:1519-1527
Nishitani, Wagner Shin; Alencar, Adriano Mesquita; Wang, Yingxiao (2015) Rapid and Localized Mechanical Stimulation and Adhesion Assay: TRPM7 Involvement in Calcium Signaling and Cell Adhesion. PLoS One 10:e0126440
Ouyang, Mingxing; Lu, Shaoying; Wang, Yingxiao (2014) Genetically encoded fluorescent biosensors for live-cell imaging of MT1-MMP protease activity. Methods Mol Biol 1071:163-74
Lu, Shaoying; Seong, Jihye; Wang, Yi et al. (2014) Decipher the dynamic coordination between enzymatic activity and structural modulation at focal adhesions in living cells. Sci Rep 4:5756
Zhou, Hua; Jakobsson, Eric (2013) Predicting protein-protein interaction by the mirrortree method: possibilities and limitations. PLoS One 8:e81100
Liao, Xiaoling; Lu, Shaoying; Wu, Yiqian et al. (2013) The effect of differentiation induction on FAK and Src activity in live HMSCs visualized by FRET. PLoS One 8:e72233
Seong, Jihye; Tajik, Arash; Sun, Jie et al. (2013) Distinct biophysical mechanisms of focal adhesion kinase mechanoactivation by different extracellular matrix proteins. Proc Natl Acad Sci U S A 110:19372-7
Lu, Shaoying; Wang, Yi; Huang, He et al. (2013) Quantitative FRET imaging to visualize the invasiveness of live breast cancer cells. PLoS One 8:e58569
Liao, Xiaoling; Lu, Shaoying; Zhuo, Yue et al. (2012) Visualization of Src and FAK activity during the differentiation process from HMSCs to osteoblasts. PLoS One 7:e42709

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