The Science Behind Cell–Material Interactions

In large-scale cell culture and regenerative medicine, microcarriers are essential for expanding adherent cells in suspension bioreactors. A 2025 study in the Chemical Engineering Journal by Tian et al. revealed that the mechanical stiffness of these carriers directly influences how human amniotic epithelial cells (hAECs) grow and maintain their identity — reshaping how we think about scalable, high-quality cell culture.

A Quick Look at hAECs

hAECs are epithelial cells derived from the amniotic membrane — the innermost layer of the placenta, normally discarded after birth.They exhibit stem-like properties, expressing markers such as OCT4, SOX2, and SSEA-4, while remaining non-tumorigenic and low-immunogenic.
Because they can differentiate into several lineages and secrete regenerative cytokines, hAECs are strong candidates for cell-based therapies.
However, they tend to lose their epithelial phenotype and slow proliferation in conventional culture — a challenge this study helps solve.

Key Findings: Softer Microcarriers, Healthier Cells

The researchers created biopolymer-based microcarriers with three stiffness levels:

  • Soft (~0.15 MPa) — mimicking the native amniotic membrane
  • Medium (~1.86 MPa) — similar to common commercial carriers
  • Stiff (~8.57 MPa) — representing rigid culture surfaces

Although surface chemistry was identical, stiffness alone changed cell behavior:

  • Soft microcarriers produced the highest proliferation and preserved epithelial morphology and markers (E-cadherin, EpCAM).
  • Medium-stiff carriers supported moderate growth but showed early epithelial-to-mesenchymal transition (EMT).
  • Stiff carriers reduced proliferation and triggered full EMT, with fibroblast-like shapes and higher CD90 and vimentin.

hAECs expanded about 28× on soft, 15× on medium, and 8× on stiff carriers, compared with 3.8× on standard 2D plastic — a clear stiffness-dependent effect.

Why Stiffness Changes Cell Behavior

The study showed that stiffness alters how hAECs remodel their own extracellular matrix (ECM) and communicate through integrin and Wnt/β-catenin pathways.

On soft microcarriers, cells produced abundant laminin-332 and collagen IV, strengthening the basement-membrane-like ECM.
This activated integrin α6β4, which maintained Wnt/β-catenin signaling, keeping the cell cycle active and preserving epithelial characteristics.
When stiffness increased, these ECM components declined, integrin signaling weakened, and β-catenin levels fell — leading to slower growth and EMT.
Blocking laminin-332 or β-catenin on soft carriers caused the same decline, confirming the mechanism.

Why Stiffness Matters for Every Cell Type

Each cell type has its own mechanical “sweet spot.”

Cell Type Optimal Stiffness (MPa) Outcome
Epithelial / stem-like cells (hAECs, ESCs) 0.1 – 1 Preserves phenotype & prevents EMT
Mesenchymal / fibroblast cells 1 – 5 Supports adhesion & differentiation
Industrial / robust lines > 5 Provides stability in bioreactors

Choosing the right stiffness improves yield, reproducibility, and product quality.

Why Choose Smart MCs Microcarriers

Smart MCs Microcarriers are designed to provide researchers with precise control over their culture environment.
Each batch can be tailored to suit different cell types and process requirements, ensuring consistent and reliable performance across applications.

Customisable Features

  • Tunable stiffness: adjustable from 3 kPa to 100 kPa to match native tissue mechanics
    Surface chemistry: modify surface charge or apply specific coatings to enhance cell attachment or signalling
  • Size and density: available in various particle sizes for different bioreactor configurations
  • Dissolvability options: choose between fully dissolvable (TrypLE or Trypsin) and non-dissolvable microcarriers depending on process needs
  • Bioreactor compatibility: suitable for spinner flasks, wave-bags, and stirred-tank systems

Smart MCs Microcarriers provide flexibility in design, enabling researchers to fine-tune their culture systems for optimal cell attachment, proliferation, and recovery.

By controlling what your cells feel, you control how they grow.
That’s the science behind high-performance, customisable microcarriers.

Buy microcarriers or contact us to discuss a stiffness profile tailored to your cell line.

Reference

Tian, J., Hao, W., Li, J., Na, X., Wang, S., Wei, W., Lu, Y., Cui, Y., Zhang, W., He, Z., Ma, G., & Zhou, W. (2025). Microcarrier stiffness controls human amniotic epithelial cells (hAECs) proliferation and epithelial-mesenchymal transition (EMT) via remodeling ECM and Wnt/β-catenin pathway. Chemical Engineering Journal, 507, 160558. https://doi.org/10.1016/j.cej.2025.160558

Disclaimer

This blog summarises findings from Tian et al., Chemical Engineering Journal (2025) to highlight the scientific importance of microcarrier stiffness. The study did not use Smart MCs microcarriers or involve Smart MCs in any way. References to Smart MCs products are included only to illustrate how these research principles are applied in our customisable microcarrier designs.