Summary
Recent studies show that liquid-liquid phase separation plays a key role in the assembly of diverse intracellular structures. However, the biophysical principles by which phase separation can be precisely localized within subregions of the cell are still largely unclear, particularly for low-abundance proteins. Here we introduce an oligomerizing biomimetic system, “Corelets”, and utilize its rapid and quantitative light-controlled tunability to map full intracellular phase diagrams, which dictate the concentrations at which phase separation occurs, and the mode of phase separation. Surprisingly, both experiments and simulations show that while intracellular concentrations may be insufficient for global phase separation, sequestering protein ligands to slowly diffusing nucleation centers can move the cell into a different region of the phase diagram, resulting in localized phase separation. This diffusive capture mechanism liberates the cell from the constraints of global protein abundance and is likely exploited to pattern condensates associated with diverse biological processes.
Sodium–glucose cotransporter (SGLT) inhibitors are new oral antidiabetes medications shown to effectively reduce glycated hemoglobin (A1C) and glycemic variability, blood pressure, and body weight without intrinsic properties to cause hypoglycemia in people with type 1 diabetes. However, recent studies, particularly in individuals with type 1 diabetes, have demonstrated increases in the absolute risk of diabetic ketoacidosis (DKA). Some cases presented with near-normal blood glucose levels or mild hyperglycemia, complicating the recognition/diagnosis of DKA and potentially delaying treatment. Several SGLT inhibitors are currently under review by the U.S. Food and Drug Administration and European regulatory agencies as adjuncts to insulin therapy in people with type 1 diabetes. Strategies must be developed and disseminated to the medical community to mitigate the associated DKA risk. This Consensus Report reviews current data regarding SGLT inhibitor use and provides recommendations to enhance the safety of SGLT inhibitors in people with type 1 diabetes.
In the originally published version of this article, the label for the vertical axis at the bottom of Figure 7H mistakenly referred to the state where D core < D IDR . The correct label should read D core R D IDR . The corrected Figure 7 is shown here and this error has now been corrected in the article online. We apologize for any confusion this error may have caused.
Suspensions of paramagnetic colloids are driven to phase separate and self-assemble in toggled magnetic fields. At field strengths above 575 A/m and toggle frequencies between 0.66 and 2 Hz, an initial gel-like, arrested network collapses into condensed, ellipsoidal aggregates. The evolution to this equilibrium structure occurs via a Rayleigh-Plateau instability. The toggle frequency ν determines the fluidity of the breakup process. At frequencies between 0.66 and 1.5 Hz, the suspension breaks up similar to a viscous, Newtonian fluid. At frequencies ν > 1.5 Hz, the network ruptures like a viscoplastic material. The field strength alters the onset time of the instability. A power law relationship emerges as the scaled frequency and field strength can be used to predict the onset of breakup. These results further aid in understanding the mechanics and dynamics of the phase separation process of suspensions of polarizable colloids in toggled external fields.
Suspensions of superparamagnetic colloids that equilibrate in a toggled magnetic field undergo a Rayleigh-Plateau instability with a characteristic wavelength λ = 600 μm for the toggle frequency ν = 0.66 Hz. The instability is suppressed when the chamber length L in the field direction is less than 2λ. The final size of the magnetic domains perpendicular to the field, D, follows a power law relation of D ∼ L(0.71±0.07). These results demonstrate the structural differences of field-directed suspensions when confined to lengths scale set by the phase separation process and can potentially be used to create self-assembled colloidal crystals with well-defined size and shape.
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