Force Transmission within Smooth Muscle Tissues

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Force Transmission within Smooth Muscle Tissues

• By
• Richard A. Meiss
• and Ramana Pidaparti
• Indiana University School of Medicine
• and Purdue University, Indianapolis

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Elements of A Smooth Muscle Tissue
1. Contractile cells
4. Radial connective tissue
2. Parallel connective tissue
5. Extracellular matrix (proteoglycans, etc.)
3. Series connective tissue
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Force Transmission at the Resting Length

• Cells generate the force and also transmit it
  throughout the tissue.
• Tissue compliance will vary with the level of
  activation.
• Overall tissue stiffness and developed force
  should vary together.
• Detaching crossbridges should produce parallel
  changes in force and stiffness.

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Force Transmission in a Smooth Muscle Tissue
Series Elastic Element
Cell 1
Cell 2
Cell 3
Contractile
cells
Connective tissue
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Experimental Methods

• Canine tracheal muscle strips
• dissected parallel to long axis of cells
• stimulated electrically
• Measured quantities
• force, length, stiffness under isometric and
  isotonic conditions
• force and/or length under servo control
• stiffness measured continuously by force
  amplitude response to sinusoidal oscillation

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Effect of Longitudinal Vibration on Isometric
Contraction

• Sinusoidal length oscillations
• high amplitude (e.g., 5 of length)
• frequencies from 5 to 50 Hz
• Crossbridges break when subjected to oscillatory
  shearing forces
• effect is stress and strain dependent
• effect is fully reversible

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Vibration applied at peak of isometric contractio
n
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Vibration applied at peak of isometric contractio
n
Note progressive exponential fall in force
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Summary of Isometric Findings

• Tissue compliance varies with the level of
  activation.
• Tissue stiffness and force vary together.
• Longitudinal vibration detaches crossbridges
• force and stiffness are reduced in parallel.
• detachment is benign and reversible.

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Mechanical Behavior at Very Short Lengths

• Mechanical conditions during contraction
• initial phase is isometric, followed by
• isotonic shortening at very low afterload.
• Stiffness is continuously measured.
• proportional to force in isometric phase
• non-linear length dependence during isotonic
  phase
• Muscle reaches an equilibrium length

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At the Start of Isotonic Shortening
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At Maximal Shortening
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As muscle shortens at constant volume, Its
diameter must Increase.
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Radial Constraint Hypothesis

• Experimental findings -
• Muscle shortens at low external force, at
  constant volume.
• Stiffness increases abruptly as limit of
  shortening is approached.
• Muscle reaches equilibrium length at high
  stiffness, low external force.
• Force / stiffness relationship depends mainly on
  muscle length.

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Radial Constraint Hypothesis

• Hypothetical explanation
• As muscle diameter increases during shortening,
  radially-oriented connective tissue is strained.
• The straining force comes from axial shortening
  of the crossbridge / myo-filament array.
• As the internal load increases, cross-bridges are
  recruited and the axial stiffness increase
  proportionally.

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Radial Constraint Hypothesis

• Hypothetical explanation (cont.)
• Tension in radial connective tissue is balanced
  by crossbridge tension.
• The incompressible extracellular matrix
  components provide the fulcrum connecting these
  two forces.
• At the short lengths, the muscle behaves as a
  Tensegrity Structure.

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Testing the Hypothesis
Detach crossbridges
Muscle elongates
Active muscle at equilibrium length forces are
balanced
Muscle shortens further
Weaken connective tissue
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Using Vibration to Detach Crossbridges
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Stiffness Is Reduced by Vibration
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Vibration Causes Exponential Decline
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Muscle Elongates Isotonically
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Negative Isometric Force
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Patterns of Post-Vibration Recovery
Isotonic
Isometric
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Prior Stiffness Predicts Recoil
External axial stiffness measures internal radial
stress
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Summary and Conclusions

• Isometric force
• Generated by active cells
• Transmitted by active cells
• Transmitted by connective tissue
• At very short lengths (and low external force),
  active and passive internal forces are balanced.
• Crossbridge/myofilament array
• Strained radial connective tissue
• Shortened muscle approximates a tensegrity
  structure when active.

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Future Directions

• Study of stresses and strains in tissue with
  cells in diagonal shear.
• Material modeling
• Electron microscopy
• Ultrastructural investigation of the
  constant-volume assumption
• Quantitative morphometry
• Monte Carlo modeling of cell size and shape with
  tissue length changes

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Future Directions (cont.)

• Biological modifications of tissue structure
• Urinary bladder hypertrophy
• Uterine changes associated with pregnancy
• Chemical modifications of tissue structure
• Enzymatic digestion of connective tissue
• Interference with integrin attachments

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Acknowledgements

• Dr. P. Sarma
• Nandhini Dhanaraj
• Department of OB/GYN, IUSM
• National Science Foundation
• Grant No. 9904610

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Experimental Apparatus
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Attaching the Muscle Strip
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From Chemical Studies

• Muscle strips were tested for shortening-dependent
  stiffness, etc.
• Strips underwent partial enzymatic digestion.
• Viability was preserved.
• Strips failed in isometric contraction.
• Strips shortened farther, and with less increase
  in longitudinal stiffness.

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Mild Collagenase Digestion
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Recoil without External Force
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Stiffness Is Reduced by Vibration