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Quantification and simulation of layer-specific mitral valve interstitial cells deformation under physiological

Chung-Hao Lee1, Christopher A Carruthers2, Salma Ayoub1

  • 1Center for Cardiovascular Simulation, Institute for Computational Engineering and Sciences (ICES), Department of Biomedical Engineering, The University of Texas at Austin, 201 East 24th Street, POB 5.236, 1 University Station C0200, Austin, TX 78712, USA.

Journal of Theoretical Biology
|March 21, 2015
PubMed
Summary

Mitral valve interstitial cells (MVICs) deform differently across leaflet layers, with fibrosa and ventricularis layers showing greater deformation. Layer structure, not cell stiffness, dictates MVIC response to stress, impacting valve function.

Keywords:
Finite element simulationsMPM imaging analysisMVIC microenvironmentMulti-level macro–micro modelingSimplified structural constitutive model

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Area of Science:

  • Biomedical Engineering
  • Cardiovascular Biology
  • Cellular Mechanics

Background:

  • Mitral valve interstitial cells (MVICs) are crucial for maintaining leaflet integrity through protein biosynthesis and degradation.
  • Tissue stress can deform MVICs, potentially impairing tissue maintenance and leading to organ-level failure.
  • Understanding the relationship between tissue loading and cellular response is vital for mitral valve research.

Purpose of the Study:

  • To investigate the layer-specific deformations of MVICs within mitral valve leaflets under controlled mechanical loading.
  • To explore the relationship between MVIC stiffness, deformation, and the mechanical/structural properties of different mitral valve tissue layers.
  • To elucidate how distinct tissue layer characteristics influence MVIC behavior and response to mechanical stimuli.

Main Methods:

  • Developed an integrated experimental-computational approach combining biaxial tension testing with multi-photon microscopy.
  • Quantified in-situ, layer-specific MVIC deformations in the four mitral valve leaflet layers.
  • Utilized a macro-micro finite element model to correlate MVIC stiffness with tissue properties.

Main Results:

  • MVICs in the fibrosa and ventricularis layers exhibited significantly greater deformation than those in the atrialis and spongiosa layers.
  • MVIC nucleus aspect ratio reached 3.3 under a maximum physiological tension of 150N/m.
  • Simulated MVIC moduli were similar across all layers (4.71-5.35kPa), indicating deformation is controlled by tissue structure, not intrinsic cell stiffness.

Conclusions:

  • MVIC deformation is primarily governed by the mechanical properties and structure of the specific mitral valve leaflet layer, not solely by intrinsic MVIC stiffness.
  • Distinct mechanical stimulatory inputs are experienced by MVICs due to the heterogeneous extracellular matrix and mechanical behaviors of the four MV leaflet layers.
  • MVICs may exhibit layer-specific responses to mechanical stimuli in both healthy and surgically altered mitral valves.