The key end-effector of acute airway narrowing in asthma is contraction of the airway smooth muscle (ASM) cell. The key motor protein that drives ASM contraction is myosin. Both the myosin-based contractile apparatus and its cytoskeletal (CSK) scaffolding are dynamic structures that are in a continuous state of remodeling, but their dynamics are not well defined. This competing renewal BRP application describes an interdisciplinary design-directed bioengineering project to fill that gap of knowledge. We propose to develop micromechanical technologies to measure cytoskeletal rheology, contractility, and remodeling. These technologies are based upon forced nano-scale motions of microbeads tightly bound to the cytoskeleton of the airway smooth muscle cell, spontaneous nano-scale motions of those same beads, and the relationship between them. Taken together, these technologies comprise a suite of novel tools that is unequalled in its ability to characterize cytoskeletal mechanics at cellular and subcellular levels. From the point of view of clinical sciences, they have bearing upon the ASM cell and the role of that cell in bronchospasm, which is our stated goal. But these technologies will have bearing as well upon any integrative (patho)physiological process that has prominent mechanical components, including vasospasm, embryonic development, pattern formation, wound healing, crawling, metastasis, invasion, and mechanotransduction. The Scientific Steering group is comprised of: Jeffrey J. Fredberg, Principal Investigator; Ben Fabry, Lead Investigator, U. Erlangen, addressing signal processing and algorithm development; Geoffrey Maksym, Lead Investigator, U. Dalhousie, addressing imaging systems and CSK remodeling; Daniel Navajas, Lead Investigator, U. Barcelona, addressing cell stretch.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Special Emphasis Panel (ZRG1-RES-D (50))
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Croxton, Thomas
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Harvard University
Public Health & Prev Medicine
Schools of Public Health
United States
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