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Multicellular aligned bands disrupt global collective cell behavior.

Mahvash Jebeli1, Samantha K Lopez1, Zachary E Goldblatt1

  • 1Biomedical Engineering Department, Worcester Polytechnic Institute, Worcester MA, USA.

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|October 28, 2022
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Summary
This summary is machine-generated.

Local cell-cell interactions in valvular interstitial cell (VIC) aggregates create dense bands, disrupting predicted global mechanical stress patterns and leading to heterogeneous cell behaviors. This emergent behavior is crucial for understanding connective tissue development and disease.

Keywords:
Collective cell behaviorMechanical stretchMicrocontact printingTraction force microscopyValvular interstitial cell

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Area of Science:

  • Cellular mechanics
  • Tissue engineering
  • Developmental biology

Background:

  • Collective cell behavior generates mechanical stresses critical for tissue development and disease.
  • Previous models of valvular interstitial cell (VIC) monolayers on circular islands correlated cell patterns with stress fields.
  • Radially symmetric models failed to predict localized regions of dense, aligned cells observed in experiments.

Purpose of the Study:

  • To investigate the emergence of heterogeneous cell behaviors over time in VIC aggregates.
  • To understand how local cell-cell interactions diverge from predicted global collective behavior.
  • To identify the mechanisms driving the formation of localized cellular structures.

Main Methods:

  • Time-lapse imaging of VIC aggregates on microcontact-printed protein islands over hours to days.
  • Measurement of cell migration, proliferation, and traction stresses.
  • Analysis of cell elongation, spread area, nuclear YAP localization, and apoptosis rates.

Main Results:

  • Elongated cells initiated strong local alignment, forming dense bands that disrupted global patterns.
  • Cells within bands showed reduced spread area and mobility, with enhanced traction stresses at band endpoints.
  • Cells in dense bands exhibited reduced proliferation, less nuclear YAP, and increased apoptosis, indicating a low-stress environment despite external forces.

Conclusions:

  • Strong local cell-cell interactions in VICs can override global collective behaviors, leading to significant heterogeneity.
  • Emergent multicellular bands disrupt predicted stress fields and influence individual cell fates.
  • This localized emergent behavior in fibroblasts is significant for connective tissue development and pathology.