Cell adhesion on substrates with variable curvature: Effects on genetic transcription processes

Area of Science:

• Biophysics
• Cell Biology
• Biomaterials Science

Background:

• Cell adhesion to substrates induces nuclear forces, altering chromatin structure and gene expression.
• Nuclear morphology changes impact molecular transport and cell differentiation.
• In vivo assessment of nuclear mechanics and substrate curvature effects remains challenging.

Purpose of the Study:

• To model nuclear stress and strain in mesenchymal stem cells (MSCs) on substrates with varying curvatures.
• To identify regions of potential adhesion-induced gene expression.
• To elucidate the impact of substrate curvature on nuclear mechanics and chromatin structure.

Main Methods:

• Developed an axisymmetric finite element model of an MSC adhering to substrates of different curvatures.
• Analyzed nuclear stress distribution and forces on chromatin fibers.
• Compared predicted forces with experimental data on chromatin condensation thresholds.

Main Results:

• Identified radial and circumferential stress fields leading to chromatin decondensation and nuclear pore opening.
• Predicted forces on chromatin fibers approached the 5 pN threshold for disrupting internucleosomal attraction.
• Convex substrates generated higher nuclear forces during early spreading compared to concave or flat substrates.

Conclusions:

• Substrate curvature significantly influences MSC nuclear mechanics and chromatin organization.
• Adhesion forces on convex substrates are closer to the chromatin decondensation threshold, potentially guiding cell fate.
• Findings offer insights for designing biomaterials to control stem cell behavior in tissue engineering and regenerative medicine.