A life off the beaten track in biomechanics: Imperfect elasticity, cytoskeletal glassiness, and epithelial unjamming

Textbook descriptions of elasticity, viscosity, and viscoelasticity fail to account for certain mechanical behaviors that typify soft living matter. Here, we consider three examples. First, strong empirical evidence suggests that within lung parenchymal tissues, the frictional stresses expressed at the microscale are fundamentally not of viscous origin. Second, the cytoskeleton (CSK) of the airway smooth muscle cell, as well as that of all eukaryotic cells, is more solid-like than fluid-like, yet its elastic modulus is softer than the softest of soft rubbers by a factor of 10(4)-10(5). Moreover, the eukaryotic CSK expresses power law rheology, innate malleability, and fluidization when sheared. For these reasons, taken together, the CSK of the living eukaryotic cell is reminiscent of the class of materials called soft glasses, thus likening it to inert materials such as clays, pastes slurries, emulsions, and foams. Third, the cellular collective comprising a confluent epithelial layer can become solid-like and jammed, fluid-like and unjammed, or something in between. Esoteric though each may seem, these discoveries are consequential insofar as they impact our understanding of bronchospasm and wound healing as well as cancer cell invasion and embryonic development. Moreover, there are reasons to suspect that certain of these phenomena first arose in the early protist as a result of evolutionary pressures exerted by the primordial microenvironment. We have hypothesized, further, that each then became passed down virtually unchanged to the present day as a conserved core process. These topics are addressed here not only because they are interesting but also because they track the journey of one laboratory along a path less traveled by.