Topology of molecular deformations induces triphasic catch bonding in selectin-ligand bonds.

Among the long-standing efforts to elucidate the physical mechanisms of protein-ligand catch bonding, particular attention has been directed at the family of selectin proteins. Selectins exhibit slip, catch-slip, and slip-catch-slip bonding, with minor structural modifications causing major changes in selectins' response to force. How can a single structural mechanism allow interconversion between these various behaviors? We present a unifying theory of selectin-ligand catch bonding, using a structurally motivated free energy landscape to show how the topology of force-induced deformations of the molecular system produces the full range of observed behaviors. We find that the pathway of bond rupture deforms in non-trivial ways, such that unbinding dynamics depend sensitively on force. This implies a severe breakdown of Bell's theory-a paradigmatic theory used widely in catch bond modeling-raising questions about the suitability of Bell's theory in modeling other catch bonds. Our approach can be applied broadly to other protein-ligand systems.

Multiple phase transitions shape biodiversity of a migrating population.

In a wide variety of natural systems, closely related microbial strains coexist stably, resulting in high levels of fine-scale biodiversity. However, the mechanisms that stabilize this coexistence are not fully understood. Spatial heterogeneity is one common stabilizing mechanism, but the rate at which organisms disperse throughout the heterogeneous environment may strongly impact the stabilizing effect that heterogeneity can provide. An intriguing example is the gut microbiome, where active mechanisms affect the movement of microbes and potentially maintain diversity. We investigate how biodiversity is affected by migration rate using a simple evolutionary model with heterogeneous selection pressure. We find that the biodiversity-migration rate relationship is shaped by multiple phase transitions, including a reentrant phase transition to coexistence. At each transition, an ecotype goes extinct and dynamics exhibit critical slowing down (CSD). CSD is encoded in the statistics of fluctuations due to demographic noise-this may provide an experimental means for detecting and altering impending extinction.