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The interplay of membrane cholesterol and substrate on vascular smooth muscle biomechanics

Hanna J Sanyour1, Alex P Rickel1, Zhongkui Hong1

  • 1Department of Biomedical Engineering, University of South Dakota, Vermillion, SD, United States.

Current Topics in Membranes
|April 10, 2021
PubMed

Insights

Atherosclerosis involves vascular smooth muscle cell (VSMC) migration, influenced by cholesterol and extracellular matrix (ECM) stiffness. Understanding these factors is crucial for cardiovascular disease (CVD) research.

Area of Science:

  • Biomedical Engineering
  • Cardiovascular Research
  • Cell Biology

Background:

  • Cardiovascular disease (CVD), particularly atherosclerosis, is a leading global cause of mortality.
  • Atherosclerosis is a chronic inflammatory condition involving cholesterol accumulation and vascular wall stiffening.
  • Vascular smooth muscle cell (VSMC) migration is a key event in atherosclerosis development.

Purpose of the Study:

  • To investigate the biomechanical effects of cellular cholesterol and extracellular matrix (ECM) stiffness on VSMC behavior.
  • To elucidate the coordinated roles of cholesterol and ECM in regulating VSMC migration and phenotypic switching.

Main Methods:

  • Utilized cell culture models to manipulate cellular cholesterol levels.
  • Employed tunable hydrogel substrates to control ECM stiffness and composition.
  • Assessed VSMC migration, proliferation, and phenotypic markers.

Main Results:

  • Cholesterol accumulation significantly altered VSMC biomechanics and migratory capacity.
  • ECM stiffness modulated VSMC responses to cholesterol, impacting cell adhesion and spreading.
  • Demonstrated a synergistic effect of cholesterol and ECM stiffness on VSMC phenotypic switching.

Conclusions:

  • Cellular cholesterol and ECM stiffness are critical regulators of VSMC biomechanics and migration in atherosclerosis.
  • The interplay between intracellular and extracellular factors dictates VSMC behavior during disease progression.
  • Findings provide novel insights into the pathogenesis of atherosclerosis and potential therapeutic targets.

Keywords:
AtherosclerosisAtomic force microscopyCell mechanicsCholesterolCytoskeletonSubstrate stiffnessVascular smooth muscle cells

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