<p>Myofibril arrangement is critical to cardiac muscle function in health and disease. Historically, analysis of the impact of myofibril organisation on force and cell contraction has relied on the assumption of uniaxial arrays. However, improvements in imaging indicate that myofibrils form complex networks, though how these networks modulate force has yet to be explored. Here, morphological analysis of sheep left-ventricular cardiomyocytes is utilised to inform a non-linear finite element model of cell contraction. Analysis of deep learning segmentations of z-discs demonstrate that myofibrils are oriented about the contraction axis (mean <InlineEquation ID="IEq1"> <EquationSource Format="TEX">\(=0.03^{\circ}\)</EquationSource> <EquationSource Format="MATHML"><math> <mrow> <mo>=</mo> <mn>0.0</mn> <msup> <mrow> <mn>3</mn> </mrow> <mrow> <mo>∘</mo> </mrow> </msup> </mrow> </math></EquationSource> </InlineEquation>) but deviate locally by up to <InlineEquation ID="IEq2"> <EquationSource Format="TEX">\(30^{\circ}\)</EquationSource> <EquationSource Format="MATHML"><math> <mrow> <mn>3</mn> <msup> <mrow> <mn>0</mn> </mrow> <mrow> <mo>∘</mo> </mrow> </msup> </mrow> </math></EquationSource> </InlineEquation> (standard deviation <InlineEquation ID="IEq3"> <EquationSource Format="TEX">\(=6.56^{\circ}\)</EquationSource> <EquationSource Format="MATHML"><math> <mrow> <mo>=</mo> <mn>6.5</mn> <msup> <mrow> <mn>6</mn> </mrow> <mrow> <mo>∘</mo> </mrow> </msup> </mrow> </math></EquationSource> </InlineEquation>). Simulations produce unique deformations for geometries informed by myofibril orientations, displaying internal rotation and off-axis deformations. Moreover, anisotropy generates shear stresses distinct from the uniaxial case, demonstrating spatial relationships that balance shear across the cell and a correlation between shear stress and z-disc orientation. These findings highlight the impact of myofibril networks on forces during cell contraction.</p>

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Cardiac myofibril networks induce shear stress

  • L. A. Murray,
  • A. P. Quinn,
  • C. Pinali,
  • D. J. Collins,
  • V. Rajagopal

摘要

Myofibril arrangement is critical to cardiac muscle function in health and disease. Historically, analysis of the impact of myofibril organisation on force and cell contraction has relied on the assumption of uniaxial arrays. However, improvements in imaging indicate that myofibrils form complex networks, though how these networks modulate force has yet to be explored. Here, morphological analysis of sheep left-ventricular cardiomyocytes is utilised to inform a non-linear finite element model of cell contraction. Analysis of deep learning segmentations of z-discs demonstrate that myofibrils are oriented about the contraction axis (mean \(=0.03^{\circ}\) = 0.0 3 ) but deviate locally by up to \(30^{\circ}\) 3 0 (standard deviation \(=6.56^{\circ}\) = 6.5 6 ). Simulations produce unique deformations for geometries informed by myofibril orientations, displaying internal rotation and off-axis deformations. Moreover, anisotropy generates shear stresses distinct from the uniaxial case, demonstrating spatial relationships that balance shear across the cell and a correlation between shear stress and z-disc orientation. These findings highlight the impact of myofibril networks on forces during cell contraction.