- Vesicle recycling in stellate astrocytic processes
Communication between astrocytes and neurons has been difficult to study because cultured astrocytes do not resemble those in vivo. Wolfes et al. develop a stellate astrocyte monoculture with physiological characteristics and find that VAMP2 and SYT7 mark distinct vesicle populations in astrocytes.
- AChR gating
Gupta et al. use single-channel electrophysiology to investigate the gating mechanism of acetylcholine receptor ion channels. They propose that channel opening starts at the M2–M3 linker and ligand-binding sites and proceeds through four brief intermediate conformations before ending with the collapse of a gate bubble.
- Structural identifiability of binding parameters
Precise mathematical descriptions of ligand–protein interactions are hindered by the inability to experimentally measure affinity and cooperativity, although these parameters can be estimated from agonist binding models. Middendorf and Aldrich present a method to determine the accuracy of parameters estimated in this way.
- Disrupted muscle maturation in Huntington’s disease
The R6/2 mouse model of Huntington’s disease exhibits reduced skeletal muscle ClC-1 currents. Miranda et al. investigate early stages of disease in these mice and find an early and progressive disruption of ClC-1 as well as altered muscle maturation based on myosin heavy chain isoform expression.
- Modeling convective flow in brain parenchyma
A “glymphatic mechanism” has been proposed to mediate convective fluid transport from para-arterial to paravenous extracellular space in the brain. Jin et al. model such a system and find that diffusion, rather than convection, can account for the transport of solutes.
- Structure and mechanism of the ATP synthase rotor
The ATP synthase is a molecular rotor that recycles ADP into ATP. Leone and Faraldo-Gómez use structural modeling to reinterpret and reconcile recent cryo-EM data for its membrane domain with other experimental evidence, gaining insights into its mechanism and the mode of inhibition by oligomycin.
- Interfilament binding of tethered molecules
Models of cellular contraction, for example, in striated muscle, usually involve mass action kinetics. Mijailovich et al. implement spatially explicit actomyosin interactions in the Monte Carlo platform MUSICO and show the extent to which myosin tethering affects other biological parameters.