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BS32 Interogating the interplay between matrix toplogy, matrix stiffness and aortic smooth muscle cell function
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  1. Teclino Afewerki1,
  2. Robert Johnson2,
  3. Reesha Solanki3,
  4. James Courtney4,
  5. Derek Warren3
  1. 1School of Pharmacy, University of East Anglia, School of Pharmacy Norwich Research Park Norwich, NFK NR4 7TJ UK
  2. 2Universit of East Anglia
  3. 3School of Pharmacy, University of East Anglia
  4. 4School of Chemical, University of Birmingham

Abstract

Background Vascular smooth muscle cells (VSMCs) are the predominant cell type in the arterial wall and normally adopt a quiescent, contractile phenotype to regulate vascular tone. VSMCs are exposed to multiple mechanical cues, including stretch and matrix stiffness, which regulate VSMC contraction. Recent studies have shown that extracellular matrix (ECM) topology and stiffness influences migration of a variety of cell types. Whilst we have extensive knowledge of how soluble factors regulate VSMC function, our understanding of the importance of matrix-derived cues is limited. Methodes In this study we use smooth and grooved polyacrylamide hydrogels of physiological and pathological stiffness, to investigate the interplay between matrix topology, matrix stiffness and VSMC function.

Results VSMCs grown on grooved hydrogels of physiological stiffness were less spread than those grown on smooth hydrogels. Traction force microscopy revealed that VSMCs on the grooved hydrogels of physiological stiffness generated enhanced traction stress compared to their counterparts on smooth hydrogels. VSMCs on grooved hydrogels of pathological stiffness still generated enhaved traction stress however, they displayed similar spreading to VSMCs grown on smooth hydrogels. Finally, we tested the impact on migration. VSMCs on grooved hydrogels of physiological stiffness displayed a reduced migrational capacity compared to their conuterparts on smooth hydrogels. However, VSMC migrational capacity remained unaltered between grooved and smooth hydrogels of pathological stiffness. Conclusion These data demonstrates that matrix topology differentially regulates VSMC function at physiological and pathological stiffness due to increased contraction of their surrounding environment. Through reducing VSMC force generation, we can potentially delay to onset of a range of age-related cardiovascular diseases.

  • stiffness
  • topology
  • Vascular smooth muscle cells

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