Striation (middle) is inefficient on too soft (left) or too hard (right) surfaces.

A small change in substrate stiffness can deter striated muscle differentiation, as shown on page 877 by Engler et al. As stiffness changes of this magnitude are not uncommon in diseased tissues, injections of stem cells may be useless unless the target environment is also treated.

Muscular dystrophy patients suffer from stiffened muscle tissue. Although muscle precursors are abundant in mdx mice, a muscular dystrophy model, they fail to regenerate injured muscle. The new article shows that this failure may be due to their overly stiff environment, which prevents skeletal muscle striation.

Skeletal muscle precursors spread, assumed a spindle shape, and fused into multinucleated cells when grown on surfaces within a wide range of stiffness. However, striation—the alignment of actin and myosin into repeated units—was blocked if the substrates were either too...

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