%0 Journal Article
%A Fan, Zhichao
%D 2019
%T 2019 Cell Reports.pdf
%U https://hra.figshare.com/articles/journal_contribution/2019_Cell_Reports_pdf/7800407
%R 10.25376/hra.7800407.v1
%2 https://hra.figshare.com/ndownloader/files/14517761
%K neutrophils
%K Integrin Mediated Adhesion
%K integrin molecules
%K lfa1
%K mac1
%K Adhesion Mechanism
%K adhesion molecules ICAM
%K microscopy imaging
%K super-resolution microscopy studies
%K Cell Biology
%K Cellular Interactions (incl. Adhesion, Matrix, Cell Wall)
%K Biophysics
%K Immunology
%K Hematology
%K Biomechanical Engineering
%X Leukocyte adhesion requires b2-integrin activation.
Resting integrins exist in a bent-closed conformation—
i.e., not extended (E) and not high affinity
(H)—unable to bind ligand. Fully activated E+H+ integrin
binds intercellular adhesion molecules (ICAMs)
expressed on the opposing cell in trans. EH transitions
to E+H+ through E+H or through EH+, which
binds to ICAMs on the same cell in cis. Spatial
patterning of activated integrins is thought to be
required for effective arrest, but no high-resolution
cell surface localization maps of activated integrins
exist. Here, we developed Super-STORM by
combining super-resolution microscopy with molecular
modeling to precisely localize activated integrin
molecules and identify the molecular patterns of activated
integrins on primary human neutrophils. At the
time of neutrophil arrest, EH+ integrins face each
other to form oriented (non-random) nanoclusters.
To address the mechanism causing this pattern, we
blocked integrin binding to ICAMs in cis, which significantly
relieved the face-to-face orientation.
%I Health Research Alliance