Understanding tissue stiffness and how cells restrict the way extracellular matrices can deform

Researchers have focused on the mechanical properties of tissues, since they are crucial for designing realistic biomimetic materials in tissue engineering and drug testing and for developing novel diagnostic techniques and medical interventions. The shear stiffness of liver, for instance, increases when the tissue is compressed, but the networks of collagen, which are presumed to determine tissue stiffness, do the opposite. Song et al. explore the mechanisms responsible for the difference.

The researchers approach tissue and cell mechanics as fundamentally different from either polymer networks or colloidal systems and show the composite material properties are not simple combinations of the parts.

“We were surprised to find that the stiffness of particles trapped in a fibrous network or cells in an extracellular matrix (ECM) is not the major factor that determines the stiffness of the particle-network composite,” said author Paul Janmey.

The researchers found even if tissues are subject to global compressions, cell-ECM interactions can cause local extensions of the fibrous ECMs, and such compression-induced extensions of the ECMs can govern tissue mechanics.

The researchers designed a way to measure stiffness by twisting a sample while it was compressed or stretched. Although stiffness depends mostly on the fibrillar ECM, the cells restrict how these fibers can bend or stretch.

Building on this work, controlling compression stiffening by inclusions might lead to more efficient lightweight packaging and bioengineered materials that more closely resemble the tissues they are designed to replace. Understanding how cells, matrix, and compression influence tissue stiffness can help interpret diagnostic assays, such as ultrasound or magnetic resonance elastography.

Source: “Cell-induced confinement effects in soft tissue mechanics,” by Dawei Song, Jordan L. Shivers, Fred MacKintosh, Alison Patteson, and Paul Janmey, Journal of Applied Physics (2021). The article can be accessed at https://doi.org/10.1063/5.0047829 .