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Effects of substrate mechanics on angiogenic capacity and nitric oxide release in human endothelial cells
Author(s) -
Jannatbabaei Atefeh,
TafazzoliShadpour Mohammad,
Seyedjafari Ehsan
Publication year - 2020
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/nyas.14326
Subject(s) - umbilical vein , stiffening , extracellular matrix , biophysics , chemistry , polydimethylsiloxane , nitric oxide , elasticity (physics) , endothelial stem cell , mechanotransduction , materials science , microbiology and biotechnology , nanotechnology , composite material , biology , biochemistry , organic chemistry , in vitro
Abstract Loss of vascular elasticity results from progressive degeneration of the extracellular matrix of elastic arteries under the effect of aging and certain diseases, including atherosclerosis. To investigate the influence of vessel wall stiffening on endothelial cell (EC) function, we seeded human umbilical vein ECs onto variably compliant polydimethylsiloxane substrates. When plated on the more compliant substrate, ECs assembled into capillary‐like structures. By contrast, they failed to form a network on stiff substrates, even in the presence of vascular endothelial growth factor (VEGF). Cell proliferation and migration increased with stiffness, while ECs released more nitric oxide (NO) on the soft substrate. Treatment with VEGF increased migration and NO release in a stiffness‐dependent manner. Atomic force microscopy measurement of cell elasticity along with actin fiber analysis revealed that ECs plated on the more compliant surface were mechanically softer, with mostly diffuse actin arrangement. Our results demonstrate that matrix stiffening induces actin reorganizations, reflected by cortical stiffening in ECs, which may lead to a decrease in their angiogenic capacity and NO release. Hence, the mechanical properties of ECs display a prognostic and therapeutic potential and might serve as a reliable biomarker of vascular function.