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Modeling cell apoptosis for simulating three-dimensional multicellular morphogenesis based on a reversible network

Satoru Okuda1,2, Yasuhiro Inoue3, Mototsugu Eiraku4

  • 1Laboratory for in vitro Histogenesis, Center for Developmental Biology (CDB), RIKEN, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan. okuda@cdb.riken.jp.

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Summary
This summary is machine-generated.

Apoptotic cell behaviors drive tissue morphogenesis by causing shrinkage and disappearance. This study models these processes in 3D, revealing how cell loss shapes tissues and induces bending or internal rearrangements.

Keywords:
Apoptotic forceCell apoptosisComputational biomechanicsMulticellular morphogenesisReversible network reconnection modelThree-dimensional vertex model

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Area of Science:

  • * Developmental Biology
  • * Computational Biology
  • * Biophysics

Background:

  • * Morphogenesis relies on coordinated cell behaviors, including apoptosis (programmed cell death).
  • * Understanding the mechanical impact of apoptotic cells in 3D tissue dynamics is crucial for development.
  • * Existing 3D vertex models, like the reversible network reconnection (RNR) model, simulate cell rearrangements but need to incorporate apoptosis.

Purpose of the Study:

  • * To develop and validate a computational model for apoptotic cell behaviors within a 3D multicellular context.
  • * To investigate the mechanical consequences of cell shrinkage and disappearance on tissue morphogenesis.
  • * To analyze how localized apoptosis influences overall tissue shape and cell organization.

Main Methods:

  • * Modeled cell apoptosis within the reversible network reconnection (RNR) framework.
  • * Cell shrinkage simulated via potential energy changes during the apoptotic phase.
  • * Cell disappearance modeled by merging polyhedrons based on RNR topological rules.
  • * Simulated morphogenesis in 3D monolayer sheets and compacted cell aggregates.

Main Results:

  • * Numerical simulations demonstrated tissue shrinkage due to successive cell apoptosis in both tested topologies.
  • * Cell number decreased while individual cell size and shape were maintained during tissue shrinkage.
  • * Localized apoptosis induced global tissue bending in monolayer sheets.
  • * Apoptosis on the surface of compacted aggregates drove internal-to-surface cell rearrangements.

Conclusions:

  • * The proposed RNR-based model successfully captures apoptotic cell behaviors in 3D multicellular systems.
  • * Modeled apoptosis effectively drives tissue size reduction and shape changes.
  • * The model provides a framework for studying the mechanical roles of cell death in 3D morphogenesis.