Viscoelastic extracellular matrix enhances epigenetic remodeling and cellular plasticity

Area of Science:

• Biomaterials Science
• Epigenetics
• Cell Biology

Background:

• Living tissues possess extracellular matrices with viscoelastic properties.
• The influence of these viscoelastic properties on chromatin regulation and the epigenome is not well understood.

Purpose of the Study:

• To investigate how matrix viscoelasticity affects nuclear architecture, epigenome, and cell reprogramming.
• To determine the impact of substrate softness and relaxation properties on these cellular changes.

Main Methods:

• Culturing fibroblasts on viscoelastic and elastic substrates with varying properties.
• Analyzing nuclear architecture, chromatin compaction, gene expression, and epigenetic marks.
• Assessing cell reprogramming efficiency into induced pluripotent stem cells and neurons.

Main Results:

• Viscoelastic substrates, particularly softer ones, induced larger nuclei and reduced chromatin compaction in fibroblasts.
• Significant differential gene expression related to cytoskeleton and nuclear function was observed.
• Slow-relaxing viscoelastic substrates decreased lamin A/C expression, enhanced nuclear remodeling, and increased euchromatin marks.
• Chromatin accessibility increased at regulatory elements for neuronal and pluripotent genes.

Conclusions:

• Matrix viscoelasticity plays a crucial role in epigenetic regulation and nuclear organization.
• Viscoelastic properties of the extracellular matrix can be leveraged to enhance cell reprogramming efficiency.
• These findings have implications for developing advanced materials for cell fate engineering and regenerative medicine.