Mimicking nuclear mechanics in stem cell adhesion on curved rigid substrates using flat soft substrates

Area of Science:

• Biomaterials Science
• Cell Biology
• Mechanobiology

Background:

• In vitro cell culture commonly uses flat substrates, which do not replicate in vivo curved mechanical environments.
• Curved substrates offer greater physiological relevance but are difficult and expensive to fabricate.

Purpose of the Study:

• To investigate if flat, soft substrates can replicate nuclear stress profiles induced by rigid curved surfaces during cell adhesion.
• To explore the role of substrate stiffness and surface curvature in cellular mechanotransduction.

Main Methods:

• Developed an axisymmetric finite element model of a human mesenchymal stem cell (hMSC).
• Simulated cell adhesion to both flat and curved substrates with varying stiffness and geometry.
• Analyzed nuclear stress states and mechanotransduction pathways.

Main Results:

• Nuclear stress from concave geometries can be mimicked by flat substrates with tuned stiffness.
• Stress patterns from convex topographies cannot be replicated by stiffness modulation alone.
• Derived a nonlinear relationship between substrate Young's modulus and curvature radius for predictive design.

Conclusions:

• Substrate stiffness partially replicates curvature-induced nuclear mechanics, but surface curvature is a critical regulator.
• Surface curvature plays a fundamental role in mechanotransduction that cannot always be replaced by stiffness.
• Provides guidelines for creating cost-effective, physiologically relevant cell culture systems.