Open AccessIntegrin nanoclusters can bridge thin matrix fibres to form cell–matrix adhesions
Author(s) -
Rishita Changede,
Haogang Cai,
Shalom J. Wind,
Michael P. Sheetz
Publication year - 2019
Publication title -
nature materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 14.344
H-Index - 483
eISSN - 1476-4660
pISSN - 1476-1122
DOI - 10.1038/s41563-019-0460-y
Subject(s) - integrin , nanoclusters , extracellular matrix , focal adhesion , biophysics , materials science , matrix (chemical analysis) , cell adhesion , adhesion , motility , microbiology and biotechnology , nanotechnology , chemistry , cell , biology , signal transduction , biochemistry , composite material
Integrin-mediated cell-matrix adhesions are key to sensing the geometry and rigidity of extracellular environments and influence vital cellular processes. In vivo, the extracellular matrix is composed of fibrous arrays. To understand the fibre geometries that are required for adhesion formation, we patterned nanolines of various line widths and arrangements in single, crossing or paired arrays with the integrin-binding peptide Arg-Gly-Asp. Single thin lines (width ≤30 nm) did not support cell spreading or formation of focal adhesions, despite the presence of a high density of Arg-Gly-Asp, but wide lines (>40 nm) did. Using super-resolution microscopy, we observed stable, dense integrin clusters formed on parallel (within 110 nm) or crossing thin lines (mimicking a matrix mesh) similar to those on continuous substrates. These dense clusters bridged the line pairs by recruiting activated but unliganded integrins, as verified by integrin mutants unable to bind ligands that coclustered with ligand-bound integrins when present in an active extended conformation. Thus, in a fibrous extracellular matrix mesh, stable integrin nanoclusters bridge between thin (≤30 nm) matrix fibres and bring about downstream consequences of cell motility and growth.