Shaping mesenchymal stem cell fate with a two-dimensional covalent triazine framework for calmodulin modulation

Area of Science:

• Biomaterials Science
• Stem Cell Biology
• Molecular Signaling

Background:

• Calmodulin (CaM) is crucial for stem cell fate, acting as a calcium sensor.
• Intracellular CaM modulation is difficult due to calcium homeostasis and limited targeting of conventional methods.

Purpose of the Study:

• To introduce a novel 2D material, CTF-Ca, for direct intracellular CaM regulation.
• To investigate CTF-Ca's effect on stem cell differentiation and CaM signaling.

Main Methods:

• Synthesis of a two-dimensional, porous, covalent triazine-based framework (CTF-Ca) under ambient conditions.
• Direct delivery of CTF-Ca into mesenchymal stem cells (MSCs) to bypass membrane calcium channels.
• Assessment of osteogenic differentiation in MSCs and myotube formation in C2C12 cells.

Main Results:

• CTF-Ca enabled direct calcium influx into MSCs, activating the Ca2+/CaM pathway.
• CTF-Ca significantly enhanced osteogenic differentiation in MSCs.
• CTF-Ca rescued osteogenic potential in CaM-inhibited MSCs and myotube formation in CaM-deficient C2C12 cells.

Conclusions:

• CTF-Ca is an effective 2D material for direct intracellular CaM modulation.
• CTF-Ca provides a novel tool for regulating stem and progenitor cell fate.
• The material demonstrates broad applicability in cell differentiation and CaM-dependent processes.