Ultrastructural Basis of Mechanotransduction in Matrix Adhesions

Information

  • Research Project
  • 8165563
  • ApplicationId
    8165563
  • Core Project Number
    P01GM098412
  • Full Project Number
    1P01GM098412-01
  • Serial Number
    98412
  • FOA Number
    PAR-10-266
  • Sub Project Id
  • Project Start Date
    9/30/2011 - 12 years ago
  • Project End Date
    8/31/2016 - 7 years ago
  • Program Officer Name
    DEATHERAGE, JAMES F.
  • Budget Start Date
    9/30/2011 - 12 years ago
  • Budget End Date
    8/31/2012 - 11 years ago
  • Fiscal Year
    2011
  • Support Year
    1
  • Suffix
  • Award Notice Date
    9/16/2011 - 12 years ago

Ultrastructural Basis of Mechanotransduction in Matrix Adhesions

DESCRIPTION (provided by applicant): The overall goal of this Program Project is to understand in detail how integrin-mediated adhesions mature and how this process determines signaling outputs. Adhesion maturation is highly dependent on physical forces, whether from endogenous myosin or applied externally through the extracellular matrix. Thus, comparison of normal adhesion ultrastructure and dynamics with responses to applied force will elucidate mechanisms of mechanotransduction. This Program Project will develop a model for mechanotransduction at matrix adhesions that integrates adhesion ultrastructure, biochemical interactions, temporal and spatial dynamics of multiprotein assemblies and signaling networks. We will analyze mechanotransduction in the context of cell migration as an important physiological output of adhesion mechanics and signaling. To achieve this, we have formed a unique team of long-standing collaborators who will implement a multifaceted experimental approach that includes molecular cell biology, biochemistry, biophysical approaches, material science, computational and mathematical analysis, and correlated high-resolution light and electron microscopy. PUBLIC HEALTH RELEVANCE: Matrix adhesions sense their mechanical environment and thereby modulate signals that regulate proliferation, differentiation, migration, and cell death. Shifts in force, therefore, can produce developmental defects and contribute to vascular and chronic inflammatory diseases, tumor formation and metastasis. Despite its importance, the mechanism underlying the transduction of force to biological signal is not understood. Our multifaceted approach will reveal its mechanistic and structural basis.

IC Name
NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
  • Activity
    P01
  • Administering IC
    GM
  • Application Type
    1
  • Direct Cost Amount
  • Indirect Cost Amount
  • Total Cost
    1573398
  • Sub Project Total Cost
  • ARRA Funded
    False
  • CFDA Code
    859
  • Ed Inst. Type
  • Funding ICs
    NIGMS:1573398\
  • Funding Mechanism
    Research Projects
  • Study Section
    ZRG1
  • Study Section Name
    Special Emphasis Panel
  • Organization Name
    SANFORD-BURNHAM MEDICAL RESEARCH INSTIT
  • Organization Department
  • Organization DUNS
    020520466
  • Organization City
    LA JOLLA
  • Organization State
    CA
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    920371005
  • Organization District
    UNITED STATES