Open AccessA discrete interface in matrix stiffness creates an oscillatory pattern of endothelial monolayer disruption
Author(s) -
Jacob A. VanderBurgh,
Archit V. Potharazu,
Samantha C. Schwager,
Cynthia A. ReinhartKing
Publication year - 2020
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.244533
Subject(s) - contractility , biophysics , stiffness , endothelial stem cell , matrix (chemical analysis) , sinusoid , biology , endothelium , stiffening , materials science , microbiology and biotechnology , composite material , endocrinology , in vitro , immunology , biochemistry
Intimal stiffening upregulates endothelial cell contractility disrupting barrier integrity; however, intimal stiffening is non-uniform. The impact of local changes in intimal stiffness on proximal and distal cell-cell interactions is unknown. To investigate the range at which matrix stiffness heterogeneities impact neighboring endothelial cells within a monolayer, we built a micropillar system with adjacent regions of stiff and compliant matrix. The stiffness interface results in an oscillatory pattern of neutrophil transendothelial migration, symmetrical about the interface and well-fit by a sinusoid function. ‘Peaks’ of the sinusoid were found to have increased cellular contractility and decreased barrier function relative to ‘troughs’ of the sinusoid. Pharmacological modulation of contractility was observed to break symmetry, altering the amplitude and wavelength of the sinusoid, indicating that contractility may regulate this effect. This work illuminates a novel biophysical phenomenon of the role of stiffness-mediated cell-matrix interactions on cell-cell interactions at a distance. Additionally, it provides insight into the range at which intimal matrix stiffness heterogeneities will impact endothelial barrier function and potentially contribute to atherogenesis.