Resolving the Stiffening-Softening Paradox in Cell Mechanics

BACKGROUND: Despite their notorious diversity, biological cells are mechanically well characterized by only a few robust and universal laws. Intriguingly, the law characterizing the nonlinear response to stretch appears self-contradictory. Various cell types have been reported to both stiffen and soften, or “fluidize” upon stretch. Within the classical paradigm of cells as viscoelastic bodies, this constitutes a paradox. PRINCIPAL FINDINGS: Our measurements reveal that minimalistic reconstituted cytoskeletal networks (F-actin/HMM) exhibit a similarly peculiar response. A mathematical model of transiently crosslinked polymer networks, the so-called inelastic glassy wormlike chain (iGwlc) model, can simulate the data and resolve the apparent contradiction. It explains the observations in terms of two antagonistic physical mechanisms, the nonlinear viscoelastic resistance of biopolymers to stretch, and the breaking of weak transient bonds between them. CONCLUSIONS: Our results imply that the classical paradigm of cells as viscoelastic bodies has to be replaced by such an inelastic mechanical model.