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Enhanced extracellular matrix remodeling due to embedded spheroid fluidization.

Tao Zhang1, Shabeeb Ameen2, Sounok Ghosh2

  • 1School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China.

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Summary
This summary is machine-generated.

We developed a computational model to study how tumor spheroids invade fibrous environments. Spheroid properties and fiber network stiffness critically influence invasion dynamics and fiber remodeling, revealing key biophysical mechanisms.

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biophysical computational modelingcell–extracellular matrix interactionsembedded spheroidmulticellular interactions

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Area of Science:

  • Biophysics
  • Computational Biology
  • Cancer Research

Background:

  • Tumor invasion is a complex biophysical process crucial for cancer metastasis.
  • Investigating tumor spheroids in fibrous environments, like collagen, offers an in vitro model for studying invasion mechanisms.

Purpose of the Study:

  • To develop a computational model predicting new mechanisms of tumor invasion.
  • To explore the interplay between spheroid rheology, fiber network stiffness, and invasion dynamics.

Main Methods:

  • Developed a 3D computational vertex model of a spheroid in a fiber network.
  • Simulated cells as deformable polyhedrons mechanically coupled to an active fiber network.
  • Tuned spheroid rheology and fiber network stiffness to observe remodeling effects.

Main Results:

  • Spheroid rheology significantly affects fiber network remodeling, with fluid-like spheroids showing greater densification and radial fiber alignment at intermediate stiffness.
  • Cellular motility drives spheroid shape fluctuations, creating feedback loops that remodel the fiber network.
  • Optimal mechanical reciprocity between spheroid and fiber network occurs within specific intermediate stiffness ranges.

Conclusions:

  • Discovered intricate morphological-mechanical interplay governing tumor spheroid invasion.
  • Both spheroid contractile strength and shape fluctuations are critical in pre-invasion stages.
  • The study quantifies the conditions for optimal spheroid-fiber network interaction during tumor invasion.