Extracellular matrix presentation modulates vascular smooth muscle cell mechanotransduction

Olga V Sazonova; Brett C Isenberg; Jacob Herrmann; Kristen L Lee; Alberto Purwada; Alex D Valentine; Jo Ann Buczek-Thomas; Joyce Y Wong; Matthew A Nugent

doi:10.1016/j.matbio.2014.11.001

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Extracellular matrix presentation modulates vascular smooth muscle cell mechanotransduction

Journal article

Peer reviewed

Extracellular matrix presentation modulates vascular smooth muscle cell mechanotransduction

Olga V Sazonova, Brett C Isenberg, Jacob Herrmann, Kristen L Lee, Alberto Purwada, Alex D Valentine, Jo Ann Buczek-Thomas, Joyce Y Wong and Matthew A Nugent

Matrix biology, Vol.41, pp.36-43

01/2015

DOI: 10.1016/j.matbio.2014.11.001

PMID: 25448408

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Abstract

The development of atherosclerosis involves phenotypic changes among vascular smooth muscle cells (VSMCs) that correlate with stiffening and remodeling of the extracellular matrix (ECM). VSMCs are highly sensitive to the composition and mechanical state of the surrounding ECM, and ECM remodeling during atherosclerosis likely contributes to pathology. We hypothesized that ECM mechanics and biochemistry are interdependent in their regulation of VSMC behavior and investigated the effect of ligand presentation on certain stiffness-mediated processes. Our findings demonstrate that substrate stiffening is not a unidirectional stimulus-instead, the influence of mechanics on cell behavior is highly conditioned on ligand biochemistry. This "stiffness-by-ligand" effect was evident for VSMC adhesion, spreading, cytoskeletal polymerization, and focal adhesion assembly, where VSMCs cultured on fibronectin (Fn)-modified substrates showed an augmented response to increasing stiffness, whereas cells on laminin (Ln) substrates showed a dampened response. By contrast, cells on Fn substrates showed a decrease in myosin light chain (MLC) phosphorylation and elongation with increasing stiffness, whereas Ln supported an increase in MLC phosphorylation and no change in cell shape with increasing stiffness. Taken together, these findings show that identical cell populations exhibit opposing responses to substrate stiffening depending on ECM presentation. Our results also suggest that the shift in VSMC phenotype in a developing atherosclerotic lesion is jointly regulated by stromal mechanics and biochemistry. This study highlights the complex influence of the blood vessel wall microenvironment on VSMC phenotype and provides insight into how cells may integrate ECM biochemistry and mechanics during normal and pathological tissue function.

Animals

Animals, Newborn

Aorta - cytology

Aorta - physiology

Cell Adhesion

Cell Proliferation

Cells, Cultured

Extracellular Matrix - physiology

Mechanotransduction, Cellular

Muscle, Smooth, Vascular - cytology

Muscle, Smooth, Vascular - physiology

Myocytes, Smooth Muscle - cytology

Myocytes, Smooth Muscle - physiology

Myosin Light Chains - metabolism

Rats

Details

Title: Subtitle: Extracellular matrix presentation modulates vascular smooth muscle cell mechanotransduction
Creators: Olga V Sazonova - Boston University
Brett C Isenberg - Boston University
Jacob Herrmann - Boston University
Kristen L Lee - Boston University
Alberto Purwada - Boston University
Alex D Valentine - Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA
Jo Ann Buczek-Thomas - Boston University
Joyce Y Wong - Boston University
Matthew A Nugent - University of Massachusetts Lowell
Resource Type: Journal article
Publication Details: Matrix biology, Vol.41, pp.36-43
DOI: 10.1016/j.matbio.2014.11.001
PMID: 25448408
NLM abbreviation: Matrix Biol
ISSN: 0945-053X
eISSN: 1569-1802
Grant note: HL072900 / NHLBI NIH HHS HL07969 / NHLBI NIH HHS HL088572 / NHLBI NIH HHS
Language: English
Date published: 01/2015
Academic Unit: Roy J. Carver Department of Biomedical Engineering
Record Identifier: 9984306834702771

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