Self-Strengthening Adhesive Force Promotes Cell Mechanotransduction

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Cellular Mechanobiology

Background:

• The native extracellular matrix (ECM) is dynamically remodeled and stiffens during tissue regeneration and disease.
• Current artificial ECMs and in vitro models are typically mechanically static, limiting their ability to mimic native biological environments.
• Understanding cellular responses to dynamic biophysical cues is crucial for advancing regenerative medicine.

Purpose of the Study:

• To design a self-strengthening polymer coating that dynamically mimics the native ECM.
• To investigate cellular responses to dynamic biophysical cues provided by the novel coating.
• To promote cell mechanical sensitivity and enhance specific cellular functions, such as osteogenic differentiation.

Main Methods:

• Incorporation of spiropyran (SP) as a dynamic anchor group to modulate the strength of cell adhesive peptide ligands.
• Utilizing spontaneous thermal merocyanine-to-spiropyran (MC-SP) isomerization for self-responsive interfacial strengthening.
• Comparing cellular responses on the self-responsive coating versus static and previous dynamic artificial ECMs.

Main Results:

• The self-responsive coating exhibits dynamic self-strengthening of interfacial interactions.
• Cells remodel the coating, activating α5β1 integrin and Rac signaling during early adhesion, followed by αvβ3 integrin and RhoA/ROCK signaling activation.
• This sequential signaling cascade enhances cellular mechanotransduction and promotes osteogenic differentiation of mesenchymal stem cells (MSCs).

Conclusions:

• A novel self-strengthening polymer coating was developed, mimicking dynamic ECM properties.
• The coating spontaneously enhances cellular mechanotransduction and osteogenic differentiation without external stimuli.
• This technology holds significant potential for applications in regenerative medicine, particularly for implanted scaffolds.