DYNAMIC STRENGTHS OF SINGLE LEUKOCYTE ADHESION BONDS
单个白细胞粘附键的动态强度
基本信息
- 批准号:6638674
- 负责人:
- 金额:$ 32.6万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2001
- 资助国家:美国
- 起止时间:2001-05-10 至 2005-03-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION (Verbatim from Applicant's Abstract): The objective of this
proposal is to develop a detailed biophysical understanding of the interactions
of leukocytes with endothelial cells by quantitating the nanoscale strengths of
single molecular bonds involved in the adhesive interactions between these
cells. As the interactions have to occur in vivo in an environment of large
hydrodynamic stresses, a repertoire of adhesive receptors @ selectins,
integrins and immunoglobulin (lg) super family receptors @ are involved in
initiation and subsequent strengthening of the adhesive interaction. While the
roles of these different receptors in the adhesive function have been well
identified, the interplay between mechanical strength, time, and chemistry of
the individual adhesive interactions at the single molecular level is largely
unknown. The present proposal attempts to bridge this gap in our understanding
by using an experimental strategy that the investigators have recently
developed to sense molecular attachments and measure single bond forces. Three
specific aims are proposed to test various hypotheses regarding the dynamics of
leukocyte adhesion to vascular endothelium. 1) To explore the hypothesis that
each receptor-ligand interaction is designed to meet different dynamic loading
requirements found in vivo, the investigators will measure the intrinsic
relations between mechanical strength and rupture time for single bonds
involving selectin and integrin receptors over many orders of magnitude in time
scale. 2) To test the hypothesis that the prominent factors governing bond
strength arise from unique arrangements of small molecular components, the
investigators will compare dynamic strength properties for selectin and
integrin interactions with site-specific ligands and ligands that have been
engineered through post-translational modification and mutation. 3) To
investigate the hypothesis that molecular strength in adhesion depends on
chemistry of receptor linkages to cytoskeletal structure as well as
ligand-receptor chemistry, the investigators will measure mechanical strengths
as a function of rupture times for biofunctional ligand bonds to receptors in
situ on cell membranes. The successful accomplishment of these aims is
critically dependent on the use of an ultrasensitive force probe with
exceptional dynamic range to sense molecular attachments and measure single
bond forces over an enormous span of time frame for detachment. The biomembrane
force probe BFP, which the investigators have recently developed, meets these
requirements. This innovative sensor can be positioned with nanoscale precision
and can quantitate forces from the weakest strength of noncovalent bonds (
about0.1 pN) up to the strength of covalent bonds (> 1000pN). Equally
essential, the BFP can stress and rupture single molecular attachments over a
span of six orders of magnitude in detachment time. By decorating the probe tip
with synthetic and recombinant ligands, the investigators plan to measure the
dynamic strengths of attachments to selectins and integrins resident on
neutrophil membranes and reconstituted on glass microspheres. These studies
will provide exciting new and novel biophysical insights into blood-vascular
cell adhesion at the molecular level, which will contibute significantly to our
understanding of receptor-mediated adhesion in normal immune function and in
pathophysiology of inflammation, tissue injury and tumor cell metastasis.
描述(逐字摘自申请人摘要):本研究的目的
项目成果
期刊论文数量(0)
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{{ truncateString('EVAN A EVANS', 18)}}的其他基金
DYNAMIC STRENGTHS OF SINGLE LEUKOCYTE ADHESION BONDS
单个白细胞粘附键的动态强度
- 批准号:
6711070 - 财政年份:2001
- 资助金额:
$ 32.6万 - 项目类别:
DYNAMIC STRENGTHS OF SINGLE LEUKOCYTE ADHESION BONDS
单个白细胞粘附键的动态强度
- 批准号:
6328238 - 财政年份:2001
- 资助金额:
$ 32.6万 - 项目类别:
DYNAMIC STRENGTHS OF SINGLE LEUKOCYTE ADHESION BONDS
单个白细胞粘附键的动态强度
- 批准号:
6537852 - 财政年份:2001
- 资助金额:
$ 32.6万 - 项目类别:
BLOOD CELL MECHANICS, SURFACE AFFINITY AND ADHESION
血细胞力学、表面亲和力和粘附力
- 批准号:
3364005 - 财政年份:1990
- 资助金额:
$ 32.6万 - 项目类别:
BLOOD CELL MECHANICS, SURFACE AFFINITY AND ADHESION
血细胞力学、表面亲和力和粘附力
- 批准号:
3364007 - 财政年份:1990
- 资助金额:
$ 32.6万 - 项目类别:
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