How Matrix Viscoelasticity Affects Cell Fate

Team Dynamic Matrices | 21 August 2025

How Matrix Viscoelasticity Affects Cell Fate

For years, the conversation about matrix mechanics in cell culture centred on a single parameter: stiffness. Stiffer substrates push mesenchymal stem cells toward bone, softer ones toward fat or neural lineages. That insight, built largely on linearly elastic hydrogels, reshaped how the field thought about the mechanical microenvironment.

But living tissue is not a linear spring. It is viscoelastic, meaning it both stores and dissipates mechanical energy over time. And over the past decade it has become clear that this time-dependent behaviour, captured most importantly by stress relaxation, is a cue in its own right, one that can be as influential as stiffness in determining what a cell becomes.

Elastic versus viscoelastic, and why it matters

In a purely elastic matrix, which is the behaviour of most conventional synthetic hydrogels, energy from the forces a cell exerts is stored in the network and held there, like a loaded spring that never releases. In a viscoelastic matrix, which is the behaviour of real tissues and of reversible, dynamically crosslinked hydrogels, that stored energy is dissipated over time through stress relaxation. The matrix yields, flows, and remodels in response to cellular forces.

This distinction is not a technicality. As a 2016 Cell Stem Cell commentary put it, stress relaxation constitutes a dynamic mechanical cue that guides signalling within the stem cell, modulating spreading, polarization, and differentiation. Cells feel not just how stiff their surroundings are, but how those surroundings respond over time to being pushed.

What the research shows

The foundational work came from Ovijit Chaudhuri and colleagues. In a landmark 2016 Nature Materials study ("Hydrogels with tunable stress relaxation regulate stem cell fate and activity"), they engineered alginate hydrogels in which stress relaxation could be modulated independently of initial stiffness. The result was striking. Faster stress relaxation enhanced the spreading, proliferation, and osteogenic differentiation of encapsulated mesenchymal stem cells in 3D. Same stiffness, different relaxation behaviour, different cell fate.

The principle has since generalised well beyond MSCs and bone. Substrate stress relaxation was shown to regulate cell spreading (Chaudhuri et al., Nature Communications, 2015), and enhanced stress relaxation promotes filopodia-mediated cell migration (Adebowale et al., Nature Materials, 2021). In a 2024 PNAS study, ECM stress relaxation was found to play a role comparable to stiffness in determining neural stem cell fate commitment, driving astrocyte differentiation through dynamic RhoA activation. Viscoelasticity and adhesion signalling were shown to control human pluripotent stem cell morphogenesis in 3D culture (Indana et al., Advanced Materials, 2021). And matrix viscoelasticity was shown to control spatiotemporal tissue organisation (Elosegui-Artola et al., Nature Materials, 2023).

The 2020 Nature review by Chaudhuri and colleagues ("Effects of extracellular matrix viscoelasticity on cellular behaviour") consolidated this body of work, establishing viscoelasticity as a fundamental regulator of cell behaviour alongside stiffness rather than subordinate to it. A 2025 review in npj Biological Physics and Mechanics extends the theme into development and disease, noting that viscoelastic properties shift in aging and pathology.

Why this matters for your culture system

If viscoelasticity shapes cell fate, then a matrix that cannot reproduce or control it is leaving out a biologically essential variable. Two practical implications follow.

First, conventional elastic hydrogels may not faithfully model in vivo behaviour, because they impose a static, energy-storing mechanical environment that no real tissue presents. Second, if you want to study the effect of stress relaxation, or simply tune it to optimise organoid formation, you need a matrix in which relaxation behaviour can be set deliberately and, ideally, independently of stiffness.

Matrigel and most natural matrices do not offer this control. Neither do older static synthetic gels. What is needed is a matrix engineered for tunable viscoelasticity.

Where DyNAtrix® fits

We built DyNAtrix around exactly this principle. It is a synthetic, DNA-crosslinked hydrogel whose stress-relaxation behaviour can be tuned across orders of magnitude, recapitulating the viscoelastic characteristics of living tissues, and it can be adjusted largely independently of the matrix's other properties. If you want to mimic tissue-like mechanics, or to investigate how stress relaxation shapes your cells, DyNAtrix turns viscoelasticity from a fixed, uncontrolled property into a designed variable. Explore DyNAtrix