editorial

Mechanobiology in harness
Understanding how cells sense and adapt to their environment, and engineering defined culture
substrates, will be central to progress in tissue engineering and regenerative medicine.
Cells are active gels. By remodelling their whole, span mechanistic, phenomenological,
cytoskeleton, they deform and migrate. In methodological and engineering aspects
fact, because the cytoskeleton is usually of the understanding and application of
coupled to the extracellular matrix by focal cellular mechanobiology. On page 631,
adhesions, cells can pull on the matrix not Pere Roca Cusachs, Xavier Trepat and
only to generate the traction forces needed colleagues show with myoepithelial cells
for migration, but also to sense its mechanical that cells can sense matrix stiffness through
properties and structure. And in addition variations in the dynamics of integrin–
to mechanical signals, cells can receive matrix bonds. In a linked News & Views
biochemical cues from small molecules, article (page 539), José García and
proteins or matrix-degradation by-products Andrés García add that these results
dissolved in the matrix or attached to it. highlight the importance of targeting specific
Both biochemical and mechanical integrins in therapies aimed to treat tissue
signals — which are transduced and regulated dysfunction. Kristi Anseth and collaborators
by the intracellular network of protein report on page 645 that stem cell fate can
interactions — are used by the cell to alter also be influenced by past mechanical
its behaviour: for example, to change shape, environments, and that such ‘mechanical
Live cells on microposts of varying stiffnesses.
migrate, reprogram itself into another cell memory’ is mediated by two transcriptional
Reproduced from Yang, M. T. et al. Nature Protoc.
and, in the case of a stem cell, differentiate co-activators known to be involved in
6, 187–213 (2011). Scale bar, 20 μm.
into a more specific cell type. critical regulatory signalling pathways.
A few of the mechanosensing, Although it is unclear how mechanical
mechanotransduction and intracellular- argue that both experimental high-throughput information is retained by the cell — as
signalling processes involved in cell materials discovery and modelling methods Jeroen Eyckmans and Christopher Chen
behaviour are fairly well understood (for that enable structure–property relationships mention in an accompanying News & Views
example, the activation of stress-sensitive will play a prime role in the search and article (page 542) — cell culture materials
transmembrane proteins such as ion channels discovery of new substrates for cell expansion. that allow for the dynamical control
or integrins, or the alignment of endothelial There would be less need for high- of substrate mechanics are poised to
cells induced by fluid shear flow), and some throughput materials discovery if we had become consequential.
are beginning to be controlled (such as the a firm grasp of how the coupling of matrix Even more puzzling is the observation,
effects, on stem cell differentiation, of matrix mechanics and biochemical factors, and their reported by Kevin Chalut and co-authors on
stiffness and topographical order at the interplay with cellular signalling, directs stem page 638, of embryonic stem cells in transition
nanoscale). However, being able to exploit the cell fate. As William Murphy, Todd McDevitt towards differentiation for which their
mechanisms of cellular mechanobiology for and Adam Engler state in a Review article on nucleus behaves as an auxetic material — that
biomedical purposes remains a dream. page 547, “the understanding of how distinct is, when stretched it expands in the transversal
Yet as Dave Dingal and Dennis Discher material characteristics combine to regulate direction, contrary to the behaviour of
conclude in a Commentary on page 532, stem cell fate is still in its infancy“. In fact, common materials. Ning Wang discusses
“with the wide range of material and analytical there exist only a handful of examples of potential explanations for the phenomenon in
technologies emerging to help the translation material-induced stem cell fate in chemically an associated News & Views (page 540).
from in vitro to in vivo, challenges in concepts defined cell culture environments. To be Cell culture is routinely performed on
and applications seem increasingly addressable sure, synthesis strategies that have enabled glass or plastic, which hardly resemble the
with suitable rigour and reproducibility”. The the systematic exploration of the effects of cells’ natural milieu. Soft substrates can be a
authors highlight the importance of both the chemistry, structure and mechanical more favourable environment, as Jianping Fu
physical and chemical factors in stem cell properties of materials on cell behaviour and colleagues show for the case of the
differentiation and self-renewal by providing have only been mastered in the last several production of functional motor neurons
examples of synergetic effects arising from years. For example, understanding how derived from human pluripotent stem
soluble factors and culture substrates (from surface texture at the nanoscale is transduced cells (page 599). In a linked News & Views
their mechanical properties or their bound by interactions with the cells’ integrin article (page 543), Emily Lowry and
factors). And as Morgan Alexander, Chris receptors — discussed by Matthew Dalby, Christopher Henderson wonder whether the
Denning and colleagues assert in a Review Nikolaj Gadegaard and Richard Oreffo in a efficacy of the soft substrates on cell yield
article on page 570, culture substrates that Review article on page 558 — requires recent can also be modulated by soluble factors.
can be scaled up to produce the billions of advances in precision nanoscale patterning Likewise, mechanical cues from synthetic
cells needed to meet the future demands of (for example, nanolithography, etching materials can influence, and may be able to
regenerative medicine and pharmaceutical or anodizing). mimic, the effects of potent soluble factors.
drug screening need to be fully synthetic, and We also include in this focus issue on The fate of mechanobiology, however, lies on
the culture conditions fully defined. They also cell culture four developments that, as a synergistically harnessing both. ❐

NATURE MATERIALS | VOL 13 | JUNE 2014 | www.nature.com/naturematerials 531

© 2014 Macmillan Publishers Limited. All rights reserved