Michael Schlierf

The actin cortex is an active polymer network underneath the plasma membrane at the periphery of mammalian cells. It is a major regulator of cell shape through the generation of active cortical tension. In addition, the cortex constitutes a mechanical shield that protects the cell during mechanical agitation. Cortical mechanics is tightly controlled by the presence of actin cross‐linking proteins that dynamically bind and unbind actin filaments. Cross‐linker actin bonds are weak non‐covalent bonds whose bond lifetime is likely affected by mechanical tension in the actin cortex making cortical composition inherently mechanosensitive. Here, a quantitative study of changes in cortex composition and turnover dynamics upon short‐lived peaks in active and passive mechanical tension in mitotic HeLa cells is presented. These findings dsclose a twofold mechanical reinforcement strategy of the cortex upon tension peaks entailing i) a direct catch‐bond mechanosensitivity of cross‐linkers filamin and α‐actinin and ii) an indirect cortical mechanosensitivity that triggers actin cortex reinforcement via enhanced polymerization of actin. Thereby a “molecular safety belt” mechanism that protects the cortex from injury upon mechanical challenges is disclosed.

Significance Outer membrane proteins (OMPs) are crucial for the survival of bacteria. The two chaperones 17-kilodalton protein (Skp) and survival factor A (SurA) play key roles in OMP maturation by keeping unfolded OMP proteins soluble in the periplasm. However, their functionalities are incompletely understood. Here, we establish connections between structural and energetic features employed by the two chaperones when interacting with unfolded OmpX. We find that expansion, accompanied with fast polypeptide chain reconfiguration, prevents unfolded OmpX from misfolding and aggregating. Moreover, chaperone interaction with unfolded OmpX is thermodynamically calibrated, allowing for a fine-tuned association of chaperones with OMPs in the adenosine triphosphate-depleted periplasm. We further discovered that Skp and SurA act together as disaggregases and are able to disassemble oligomeric OMP aggregates, revealing remarkable functionalities of this periplasmic chaperone system.