Connecting Transitions in Galaxy Properties to Refueling

We relate transitions in galaxy structure and gas content to refueling, here defined to include both the external gas accretion and the internal gas processing needed to renew reservoirs for star formation. We analyze two z = 0 data sets: a high-quality ~200 galaxy sample (the Nearby Field Galaxy Survey, data release herein) and a volume-limited ~3000 galaxy sample with reprocessed archival data. Both reach down to baryonic masses ~10^9 M_☉ and span void-to-cluster environments. Two mass-dependent transitions are evident: (1) below the "gas-richness threshold" scale (V ~ 125 km s^(–1)), gas-dominated quasi-bulgeless Sd-Im galaxies become numerically dominant; while (2) above the "bimodality" scale (V ~ 200 km s^(–1)), gas-starved E/S0s become the norm. Notwithstanding these transitions, galaxy mass (or V as its proxy) is a poor predictor of gas-to-stellar mass ratio M_(gas)/M_*. Instead, M_(gas)/M_* correlates well with the ratio of a galaxy's stellar mass formed in the last Gyr to its preexisting stellar mass, such that the two ratios have numerically similar values. This striking correspondence between past-averaged star formation and current gas richness implies routine refueling of star-forming galaxies on Gyr timescales. We argue that this refueling underlies the tight M_(gas)/M_* versus color correlations often used to measure "photometric gas fractions." Furthermore, the threshold and bimodality scale transitions reflect mass-dependent demographic shifts between three refueling regimes—accretion-dominated, processing-dominated, and quenched. In this picture, gas-dominated dwarfs are explained not by inefficient star formation but by overwhelming gas accretion, which fuels stellar mass doubling in ≾1 Gyr. Moreover, moderately gas-rich bulged disks such as the Milky Way are transitional, becoming abundant only in the narrow range between the threshold and bimodality scales

Physics of the nuclear pore complex: Theory, modeling and experiment

The hallmark of eukaryotic cells is the nucleus that contains the genome, enclosed by a physical barrier known as the nuclear envelope (NE). On the one hand, this compartmentalization endows the eukaryotic cells with high regulatory complexity and flexibility. On the other hand, it poses a tremendous logistic and energetic problem of transporting millions of molecules per second across the nuclear envelope, to facilitate their biological function in all compartments of the cell. Therefore, eukaryotes have evolved a molecular "nanomachine" known as the Nuclear Pore Complex (NPC). Embedded in the nuclear envelope, NPCs control and regulate all the bi-directional transport between the cell nucleus and the cytoplasm. NPCs combine high molecular specificity of transport with high throughput and speed, and are highly robust with respect to molecular noise and structural perturbations. Remarkably, the functional mechanisms of NPC transport are highly conserved among eukaryotes, from yeast to humans, despite significant differences in the molecular components among various species. The NPC is the largest macromolecular complex in the cell. Yet, despite its significant complexity, it has become clear that its principles of operation can be largely understood based on fundamental physical concepts, as have emerged from a combination of experimental methods of molecular cell biology, biophysics, nanoscience and theoretical and computational modeling. Indeed, many aspects of NPC function can be recapitulated in artificial mimics with a drastically reduced complexity compared to biological pores. We review the current physical understanding of the NPC architecture and function, with the focus on the critical analysis of experimental studies in cells and artificial NPC mimics through the lens of theoretical and computational models. We also discuss the connections between the emerging concepts of NPC operation and other areas of biophysics and bionanotechnology

Programmable de novo designed coiled coil-mediated phase separation in mammalian cells

Abstract Membraneless liquid compartments based on phase-separating biopolymers have been observed in diverse cell types and attributed to weak multivalent interactions predominantly based on intrinsically disordered domains. The design of liquid-liquid phase separated (LLPS) condensates based on de novo designed tunable modules that interact in a well-understood, controllable manner could improve our understanding of this phenomenon and enable the introduction of new features. Here we report the construction of CC-LLPS in mammalian cells, based on designed coiled-coil (CC) dimer-forming modules, where the stability of CC pairs, their number, linkers, and sequential arrangement govern the transition between diffuse, liquid and immobile condensates and are corroborated by coarse-grained molecular simulations. Through modular design, we achieve multiple coexisting condensates, chemical regulation of LLPS, condensate fusion, formation from either one or two polypeptide components or LLPS regulation by a third polypeptide chain. These findings provide further insights into the principles underlying LLPS formation and a design platform for controlling biological processes

Molecular Determinants of Tubulin’s C‑Terminal Tail Conformational Ensemble

Tubulin is important for a wide variety of cellular processes including cell division, ciliogenesis, and intracellular trafficking. To perform these diverse functions, tubulin is regulated by post-translational modifications (PTM), primarily at the C-terminal tails of both the α- and β-tubulin heterodimer subunits. The tubulin C-terminal tails are disordered segments that are predicted to extend from the ordered tubulin body and may regulate both intrinsic properties of microtubules and the binding of microtubule associated proteins (MAP). It is not understood how either interactions with the ordered tubulin body or PTM affect tubulin’s C-terminal tails. To probe these questions, we developed a method to isotopically label tubulin for C-terminal tail structural studies by NMR. The conformational changes of the tubulin tails as a result of both proximity to the ordered tubulin body and modification by mono- and polyglycine PTM were determined. The C-terminal tails of the tubulin dimer are fully disordered and, in contrast with prior simulation predictions, exhibit a propensity for β-sheet conformations. The C-terminal tails display significant chemical shift differences as compared to isolated peptides of the same sequence, indicating that the tubulin C-terminal tails interact with the ordered tubulin body. Although mono- and polyglycylation affect the chemical shift of adjacent residues, the conformation of the C-terminal tail appears insensitive to the length of polyglycine chains. Our studies provide important insights into how the essential disordered domains of tubulin function