BASEMENT MEMBRANE SELF-ASSEMBLY AND STRUCTURE

Project Details

Description

Basement membranes (BMs) are sheet-like supportive frameworks to which
cells adhere, which affect cell growth and differentiation and which serve
as important permeability barriers to the passage of large molecules.
There are several unique macromolecules which are intrinsic to these
structures and which cooperatively assemble into a three-dimensional
matrix: they include type IV collagen, laminin, proteoheparan sulfate,
nidogen and probably entactin. Despite the limited number of component
building blocks, structural heterogeneity can be found in comparing BMs.
Furthermore, alterations in the structure and function of BMs are seen in a
number of diseases of which diabetes mellitus is a commonly cited example. Basement membrane assembly and structure will be studied in order to
address the following questions: First, is the information for
three-dimensional structure contained only in the BM components
themselves? Second, given a limited number of building blocks, can BM
heterogeneity be explained by the concept of assembly polymorphism (the
ability of macromolecules to assemble into different heteropolymeric
structures depending on environmental conditions)? Third, can the
molecular structure explain the selective permeability function? Fourth,
can a sound molecular basis for assembly and structure be developed in
order to test hypotheses that explain the mechanisms and
structural/functional alterations which occur in pathological states? Two different but complementary approaches will be used. First, building
upon previous work and using a combination of biophysical, biochemical and
rotary shadow EM techniques, in vitro homo/heteropolymer formation will be
examined with respect to thermodynamics, stoichiometry and domain
specificity of interaction with particular focus on the contributions of
laminin, proteoheparan sulfate-laminin and proteoheparan sulfate-collagen
to assembly. Second, the supramolecular organization of selected
accessible BMs will be probed by EM rotary shadow and xray diffraction of
BM surfaces decorated with metal-tagged specific antibodies or treated by
selective enzymatic degradation. These studies will be used to construct
models for the assembly, structure and resulting function of these matrices.
StatusActive
Effective start/end date1/1/866/30/23

Funding

  • National Institutes of Health: $292,340.00
  • National Institutes of Health: $292,340.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $173,502.00
  • National Institutes of Health: $278,082.00
  • National Institutes of Health: $255,839.00
  • National Institutes of Health: $192,584.00
  • National Institutes of Health: $248,388.00
  • National Institutes of Health: $285,470.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $357,750.00
  • National Institutes of Health: $345,825.00
  • National Institutes of Health: $175,686.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $345,825.00
  • National Institutes of Health: $345,825.00
  • National Institutes of Health: $165,797.00
  • National Institutes of Health: $272,548.00
  • National Institutes of Health: $275,301.00
  • National Institutes of Health: $303,082.00
  • National Institutes of Health: $272,548.00
  • National Institutes of Health: $277,191.00
  • National Institutes of Health: $241,154.00
  • National Institutes of Health
  • National Institutes of Health: $328,883.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $345,825.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $357,750.00

ASJC

  • Medicine(all)

Fingerprint Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.