Large-Scale Nanofiber Manufacturing| Cellular Spatial sensing Determines Cell MechanotransductionActivity on the Aligned Nanofibers

Researcher Wei Qiang from Sichuan University in "Small": Cell "Body Size" Determines Mechanotransduction

Fiber-based tissue engineering has become crucial for designing scaffolds that closely mimic the extracellular matrix (ECM). The ECM consists of complex fiber networks with varying alignment patterns. Electrospun nanofibers are widely used as scaffold materials in tissue engineering, but how cells respond to differently aligned fibers remains controversial. Some studies suggest aligned fibers promote osteogenic differentiation, while others show random alignment works better. This contradiction stems from insufficient understanding of how cells perceive fiber spatial characteristics.From a mechanobiological perspective, regardless of external conditions, cell behavior is primarily governed by intracellular traction forces. These forces are generated through actin stress fibers and transmitted to the ECM via focal adhesions, then converting mechanical signals into nuclear responses that influence chromatin structure and gene expression. This mechanical feedback loop regulates cell morphology, proliferation, and differentiation. Thus, understanding how fiber alignment modulates these mechanotransduction signals is essential.

Recently, Researcher Wei Qiang's team from Sichuan University used polycaprolactone (PCL) electrospun fibers with controlled alignment to simulate ECM structures, investigating how fiber arrangement regulates mechanotransduction and cell behavior. Results show cell size plays a key role in determining spatial relationships between cells and fibers, directly affecting mechanotransduction. Larger cells spanning multiple fibers exhibit enhanced spreading and increased mechanotransduction, while smaller cells confined within fiber gaps show reduced mechanical signaling.Although aligned fibers consistently induce cell polarization along fiber direction, the underlying mechanisms vary with cell size, leading to distinct behaviors. By adjusting cell-fiber spatial relationships, the study demonstrates their critical role in regulating cell function. These findings provide key theoretical support for designing precise bioinspired scaffolds. The work, titled "Cellular Spatial Sensing Determines Cell Mechanotransduction Activity on Aligned Nanofibers," was published in "Small".

Research Highlights:

1. Size advantage: When cell width exceeds 5 times the fiber gap (≈40 μm), cells can span multiple fibers, forming robust stress fibers that significantly enhance mechanotransduction activity. Smaller cells (width <20 μm) remain confined within fiber gaps with limited mechanical signaling.

2. Spatial positioning determines cell fate: Using 3D imaging, the team first revealed two spatial patterns - "outward cells" spanning fiber surfaces and "inward cells" trapped in gaps. The former show higher mechanotransduction efficiency by forming mature focal adhesions.

3. Semi-aligned fiber breakthrough: The team innovatively developed semi-aligned fiber networks that help small cells overcome spatial constraints by optimizing fiber gaps and orientation, significantly improving their mechanotransduction capacity and providing new material strategies for directional tissue regeneration.

Figure 1. Preparation, characterization of aligned electrospun PCL fibers and their effects on six cell types' morphology.

Figure 2. Cell traction forces and mechanotransduction on controllably aligned electrospun fibers.

Figure 3. Cell morphology and alignment on aligned fibers.

Figure 4. Two mechanisms of cell adhesion and polarization on aligned fibers.

Figure 5. Cell mechanotransduction after adjusting spatial relationships with fibers.

From micro-scale cells to macro-scale tissues, this "cellular spatial science" reaffirms that "small dimensions shape big futures." We anticipate this "cellular architecture" research will soon translate into clinical tools, pioneering a new era for regenerative medicine!