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Shaping 3D minimal model tissues with mechanical constraints to orchestrate muscle differentiation
Irène Nagle1, Lorijn van der Spek1, Paul Gesenhues1
1Université Paris Cité, Centre National de la Recherche Scientifique (CNRS), UMR 7057, Matière et Systèmes Complexes, Paris, France.
Communications Biology
|November 29, 2025
Summary
Mechanical forces guide cell alignment and tissue organization during development. This 3D cellular alignment is essential for myoblast differentiation, with physical forces enhancing its efficiency.
Area of Science:
- Biophysics
- Developmental Biology
- Cellular Mechanics
Background:
- Biological tissues develop complex shapes through integrated cues, with mechanics playing a key role.
- While biochemical factors in differentiation are known, the impact of physical forces and tissue topology is less understood.
Purpose of the Study:
- To investigate the interplay between 3D cellular alignment, mechanical stress, and myoblast differentiation.
- To determine if mechanical forces influence tissue self-organization and myogenesis.
Main Methods:
- Utilizing self-organized C2C12 myoblast aggregates subjected to controlled mechanical stretching.
- Analyzing cellular organization, actin orientation, and differentiation patterns in 3D.
- Employing single-molecule fluorescent hybridization to map alignment and differentiation hotspots.
Main Results:
- Cells spontaneously formed multilayered, actin-oriented tissues under mechanical stress.
- Mechanical forces promoted long-range 3D tissue organization and myogenesis.
- Differentiation was concentrated in regions of high stress and cellular alignment, particularly at the tissue core and surface.
Conclusions:
- 3D cellular alignment is a prerequisite for efficient myoblast differentiation.
- Mechanical constraints significantly enhance the efficiency of differentiation in developing tissues.
- Physical forces are critical drivers of self-organized tissue architecture and organ formation.
