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Integration of Mechanotransduction and T-cell Activation Thresholds: Understanding of the Effects of Mechanical Forces on Assembly and Integration of Signal Transduction Machinery During T-cell Activation (ARC00XX166)
Research Area:
Cell and molecular biology

The influence of mechanical loading on cell structure and behavior is on the cutting edge of current cell biology research. Space flight has been postulated to alter mechanical loads on cells and it is known to alter cellular behavior. T-cell activation is known to be affected during space flight, but the association with altered mechanical environments remains unclear. Our hypothesis is that alterations in the mechanical environment to which T-cell are exposed can directly modulate the cell's ability to polarize and to integrate the signal transduction machinery. This results in a shift in the activation threshold due to altered assembly and effectiveness of cellular signaling systems. To characterize this phenomenon, primary T-cells will be activated in a cell-contact dependent manner under a variety of mechanical loading scenarios. Culture conditions include standard 1xG culture conditions, clinorotation (a ground-based culture model that provides elements of the physical environment present in cell culture during space flight) and controlled induction of mechanical loads. These experiments specifically will assess: 1) the effect of the mechanical forces on the activation response of T-cells, 2) morphological assessment of cell contact and polarization by environmental scanning electron microscopy/ESEM, 3) assessment of the integration of the mechanosensing and signaling components of the cell using confocal microscopy, and 4) proteomic assessment of early and downstream signal transduction events. This approach represents a novel application of biochemical, morphological and mechanical assessment of T-cell activation and will provide a significant insight into the behavior of T-cells under changing environmental conditions. A more fundamental understanding of how T-cells integrate the signals during activation and how the external mechanical environment affects the threshold of activation will provide a mechanistic framework for interpretation of space flight and Earth-based immunology studies.

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Data Information
Data Availability
Archive is complete. No data sets are available for this experiment. Please Contact LSDA if you know of available data for this investigation.

Mission/Study Information
Mission Launch/Start Date Landing/End Date Duration
Ground 05/01/2009 In Progress

Additional Information
Managing NASA Center
Ames Research Center (ARC)
Responsible NASA Representative
Ames Research Center LSDA Level 3
Project Manager: Martha Del Alto
Institutional Support
National Aeronautics and Space Administration (NASA)
Proposal Date
Proposal Source
2012 Space Biology NNH12Z