Airway contractility in the precision-cut lung slice after cryopreservation.

An emerging tool in airway biology is the precision-cut lung slice (PCLS). Adoption of the PCLS as a model for assessing airway reactivity has been hampered by the limited time window within which tissues remain viable. Here we demonstrate that the PCLS can be frozen, stored long-term, and then thawed for later experimental use. Compared with the never-frozen murine PCLS, the frozen-thawed PCLS shows metabolic activity that is decreased to an extent comparable to that observed in other cryopreserved tissues but shows no differences in cell viability or in airway caliber responses to the contractile agonist methacholine or the relaxing agonist chloroquine. These results indicate that freezing and long-term storage is a feasible solution to the problem of limited viability of the PCLS in culture.

The actin regulator zyxin reinforces airway smooth muscle and accumulates in airways of fatal asthmatics.

Bronchospasm induced in non-asthmatic human subjects can be easily reversed by a deep inspiration (DI) whereas bronchospasm that occurs spontaneously in asthmatic subjects cannot. This physiological effect of a DI has been attributed to the manner in which a DI causes airway smooth muscle (ASM) cells to stretch, but underlying molecular mechanisms-and their failure in asthma-remain obscure. Using cells and tissues from wild type and zyxin-/- mice we report responses to a transient stretch of physiologic magnitude and duration. At the level of the cytoskeleton, zyxin facilitated repair at sites of stress fiber fragmentation. At the level of the isolated ASM cell, zyxin facilitated recovery of contractile force. Finally, at the level of the small airway embedded with a precision cut lung slice, zyxin slowed airway dilation. Thus, at each level zyxin stabilized ASM structure and contractile properties at current muscle length. Furthermore, when we examined tissue samples from humans who died as the result of an asthma attack, we found increased accumulation of zyxin compared with non-asthmatics and asthmatics who died of other causes. Together, these data suggest a biophysical role for zyxin in fatal asthma.

Illuminating human health through cell mechanics.

Cells reside in mechanically rich and dynamic microenvironments, and the complex interplay between mechanics and biology is widely acknowledged. Recent research has yielded insights linking the mechanobiology of cells, human physiology, and pathophysiology. In particular, we have learned of the cell's astounding ability to sense and respond to its mechanical microenvironment. This seemingly innate behaviour of the cell has driven efforts to characterise precisely the cellular behaviour from a mechanical viewpoint. Here we present an overview of technologies used to probe cell mechanical and material properties, how they have led to the discovery of seemingly strange cellular mechanical behaviours, and their influential role in health and disease, including asthma, cancer, and glaucoma. The properties reviewed here have implications in physiology and pathology and raise questions that will fuel research opportunities for years to come.