Linked Life Data

20725043

Source:http://linkedlifedata.com/resource/pubmed/id/20725043

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7309
pubmed:dateCreated
2010-8-20
pubmed:abstractText
Haemostasis in the arteriolar circulation mediated by von Willebrand factor (VWF) binding to platelets is an example of an adhesive interaction that must withstand strong hydrodynamic forces acting on cells. VWF is a concatenated, multifunctional protein that has binding sites for platelets as well as subendothelial collagen. Binding of the A1 domain in VWF to the glycoprotein Ib alpha subunit (GPIbalpha) on the surface of platelets mediates crosslinking of platelets to one another and the formation of a platelet plug for arterioles. The importance of VWF is illustrated by its mutation in von Willebrand disease, a bleeding diathesis. Here, we describe a novel mechanochemical specialization of the A1-GPIbalpha bond for force-resistance. We have developed a method that enables, for the first time, repeated measurements of the binding and unbinding of a receptor and ligand in a single molecule (ReaLiSM). We demonstrate two states of the receptor-ligand bond, that is, a flex-bond. One state is seen at low force; a second state begins to engage at 10 pN with a approximately 20-fold longer lifetime and greater force resistance. The lifetimes of the two states, how force exponentiates lifetime, and the kinetics of switching between the two states are all measured. For the first time, single-molecule measurements on this system are in agreement with bulk phase measurements. The results have important implications not only for how platelets bound to VWF are able to resist force to plug arterioles, but also how increased flow activates platelet plug formation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1476-4687
pubmed:author
pubmed:issnType
Electronic
pubmed:day
19
pubmed:volume
466
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
992-5
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
A mechanically stabilized receptor-ligand flex-bond important in the vasculature.
pubmed:affiliation
Immune Disease Institute, Children's Hospital Boston and Department of Pathology, Harvard Medical School, 3 Blackfan Circle, Boston, Massachusetts 02115, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural