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Spatial patterning of cell proliferation and differentiation depends on mechanical stress magnitude

Authors
Journal
Journal of Biomechanics
0021-9290
Publisher
Elsevier
Publication Date
Volume
42
Issue
11
Identifiers
DOI: 10.1016/j.jbiomech.2009.04.033
Keywords
  • Cell Aggregate
  • Finite Element Analysis
  • Mechanical Stress
  • Proliferation
  • Differentiation

Abstract

Abstract Mechanical stress has been proposed as a major regulator of tissue morphogenesis; however, it remains unclear what is the exact mechanical signal that leads to local tissue pattern formation. We explored this question by using a micropatterned cell aggregate model in which NIH 3T3 fibroblasts were cultured on micropatterned adhesive islands and formed cell aggregates (or “cell islands”) of triangular, square, and circular shapes. We found that the cell islands generated high levels of mechanical stresses at their perimeters compared to their inner regions. Regardless of the shape of cell islands, the mechanical stress patterns corresponded to both cell proliferation and differentiation patterns, meaning that high level of cell proliferation and differentiation occurred at the locations where mechanical stresses were also high. When mechanical stretching was applied to cell islands to elevate overall mechanical stress magnitudes, cell proliferation and differentiation generally increased with the relatively higher mechanical stresses, but neither cell proliferation nor differentiation patterns followed the new mechanical stress pattern. Thus, our findings indicate that a certain range of mechanical stress magnitudes, termed window stress threshold, drives formation of cell proliferation and differentiation patterns and hence possibly functions as a morphogenetic cue for local tissue pattern formation in vivo.

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