How DyNAtrix® Guides the Fate of Stem Cells, Organoids and Tissues

Team Dynamic Matrices | 15 October 2025

This post is about our own product, so we will be specific about what it does, what we have shown, and what we have not yet shown.

The premise: mechanics are a fate signal

Stem cell fate is not decided by genetics and soluble factors alone. The mechanical and biochemical cues of the surrounding matrix can be as potent as growth factors. Engler et al. (Cell, 2006) showed MSCs on soft substrates go neural, on intermediate ones muscle, on stiff ones bone, with no change in medium. Chaudhuri et al. (Nature Materials, 2016) showed stress relaxation does the same at constant stiffness. Dupont et al. (Nature, 2011) identified YAP/TAZ as the transducer. These are among the most replicated results in the field.

The problem: development happens in a changing matrix

A fixed-stiffness gel captures one moment. Real differentiation happens in a matrix that evolves: the intestinal niche softens as crypts form (Gjorevski et al., Nature, 2016), the developing heart stiffens roughly tenfold as it matures (Young and Engler, Biomaterials, 2011), and neural tissue softens over development. Multi-stage differentiation protocols implicitly need different mechanics at different stages.

With conventional materials the only way to change mechanics is to recover cells and re-embed them in a new gel. That step breaks cell-matrix connections, exposes cells to enzymatic or mechanical stress, introduces operator variability, and, as Yang et al. (Nature Materials, 2014) showed, leaves a mechanical memory from the previous substrate that skews what happens in the next one.

What DyNAtrix does differently

DyNAtrix is a fully synthetic, animal-free hydrogel: a linear polyacrylamide backbone crosslinked by short synthetic DNA duplexes, with adhesion peptides (RGD, GFOGER and others) attached separately. Three properties follow from the DNA crosslinks.

Stiffness and stress relaxation are independent dials. Polymer content sets stiffness. The crosslinker sequence and length set the relaxation time, over about five orders of magnitude. You can hold one and vary the other.

Mechanics can be changed in place. Adding a complementary DNA strand increases crosslinking and stiffens the gel around living cells. Adding a displacing strand softens it. Both happen at 37 °C in medium, with no light source, no temperature shift, no re-embedding. A staged protocol becomes a series of pipetting steps into the same well.

Cells come out intact. A nuclease dissolves the gel in minutes without touching the cells, so recovery for passaging, sorting or sequencing is gentle. In our hands recovery viability is high.

What we have validated

In Peng et al. (Nature Nanotechnology, 2023) and subsequent work:

• Human MSCs: lineage response to stress relaxation at fixed stiffness, consistent with the Chaudhuri alginate results
• Human iPSCs: maintenance and 3D morphogenesis, with dependence on the relaxation window
• Trophoblast organoids: formation and long-term culture
• MDCK kidney cysts: polarised lumen formation
• Long-term culture beyond 60 days without matrix replacement
• In situ stiffening of cultures by strand addition without loss of viability

Ongoing work in our lab and with partners includes brain organoids, long-term primary cell culture, and breast cancer organoids where we use the DNA crosslinks as a force probe to read the mechanical behaviour of metastatic cells.

What we have not yet validated, and what we tell customers

Effectiveness varies by cell type and protocol. We do not yet have data for every lineage, and for some the required adhesion ligands are not yet enumerated by anyone. If you are planning a staged differentiation, talk to us about the specific stages and the mechanics you want at each; we will tell you whether we have data, whether a pilot is needed, and what the pilot should look like. We would rather lose a sale than ship a kit that fails in your hands.

A staged protocol, in outline

For a protocol that wants expansion at one stiffness and differentiation at another:

1. Embed cells in DyNAtrix at the expansion setting (for intestinal-type expansion, around 1 to 1.5 kPa with moderate relaxation).
2. Culture to the transition point.
3. Add the softening strand directly to the medium; the gel reaches its new modulus within hours.
4. Switch medium to the differentiation formulation.
5. At the end, add nuclease, recover cells, analyse.

No transfer, no second gel, no memory from a prior substrate.