Microtubules form by progressively faster tubulin accretion, not by nucleation–elongation

Microtubules are dynamic polymers that play fundamental roles in all eukaryotes. Despite their importance, how new microtubules form is poorly understood. Textbooks have focused on variations of a nucleation–elongation mechanism in which monomers rapidly equilibrate with an unstable oligomer (nucleus) that limits the rate of polymer formation; once formed, the polymer then elongates efficiently from this nucleus by monomer addition. Such models faithfully describe actin assembly, but they fail to account for how more complex polymers like hollow microtubules assemble. Here, we articulate a new model for microtubule formation that has three key features: (1) microtubules initiate via rectangular, sheet-like structures that grow faster the larger they become; (2) the dominant pathway proceeds via accretion, the stepwise addition of longitudinal or lateral layers; and (3) a “straightening penalty” to account for the energetic cost of tubulin’s curved-to-straight conformational transition. This model can quantitatively fit experimental assembly data, providing new insights into biochemical determinants and assembly pathways for microtubule nucleation.

Mini Review: Transport of Hydrophobic Polymers Into the Plant Apoplast

The plant apoplast contains the four hydrophobic polymer, lignin, suberin, cutin, and cutan, that are crucial for stress resistance, controlling solute diffusion, and strengthening the cell wall. Some of these polymers are widely used in industry and daily life products, such as all wood-containing goods (lignin) and wine cork (suberin). Despite the importance of these polymers, several aspects of their formation remain unknown. This mini review highlights technical bottlenecks in the current research and summarizes recent insights into the precursor transmembrane transport, an essential step in the polymer formation. We also briefly discuss how some of the remaining knowledge gaps can be closed and how a better understanding of these biopolymers will benefit other research fields.

In-Situ Spectroelectrochemical Study of Conductive Polyaniline Forms for Sensor Applications

Our contribution focuses on a correlative study of polyaniline (PANI) electropolymerisation and UV/VIS spectroscopy. PANI was prepared via electro-oxidation using a potentiodynamic method on commercial gold screen-printed electrodes (Au-SPE). By using an in-situ spectroelectrochemical method, the development of the polymer was observed from monomer, monomer oxidation to final polymer formation and its transformations between the oxidation forms. The results confirm the spontaneous doping of the polymer during the polymerisation, the instability of leucoemeraldine form in air and its two-stage oxidation to emeraldine form. The final conductive PANI deposited on Au-SPE will be used as sensor element for the detection of toxic organic compounds.

VZHE-039, a novel antisickling agent that prevents erythrocyte sickling under both hypoxic and anoxic conditions

Sickle cell disease (SCD) results from a hemoglobin (Hb) mutation βGlu6 → βVal6 that changes normal Hb (HbA) into sickle Hb (HbS). Under hypoxia, HbS polymerizes into rigid fibers, causing red blood cells (RBCs) to sickle; leading to numerous adverse pathological effects. The RBC sickling is made worse by the low oxygen (O2) affinity of HbS, due to elevated intra-RBC concentrations of the natural Hb effector, 2,3-diphosphoglycerate. This has prompted the development of Hb modifiers, such as aromatic aldehydes, with the intent of increasing Hb affinity for O2 with subsequent prevention of RBC sickling. One such molecule, Voxelotor was recently approved by U.S. FDA to treat SCD. Here we report results of a novel aromatic aldehyde, VZHE-039, that mimics both the O2-dependent and O2-independent antisickling properties of fetal hemoglobin. The latter mechanism of action—as elucidated through crystallographic and biological studies—is likely due to disruption of key intermolecular contacts necessary for stable HbS polymer formation. This dual antisickling mechanism, in addition to VZHE-039 metabolic stability, has translated into significantly enhanced and sustained pharmacologic activities. Finally, VZHE-039 showed no significant inhibition of several CYPs, demonstrated efficient RBC partitioning and high membrane permeability, and is not an efflux transporter (P-gp) substrate.

Experimental Evidence for a General Model of Modulated MOF Nanoparticle Growth

<p>Nanoparticles of metal-organic frameworks (nanoMOFs) boast superior properties compared to their bulk analogs, yet little is known about how common synthetic parameters dictate particle sizes. Here, we provide experimental evidence for the “seesaw” model of nanoMOF growth. Solution acidity, ligand excess, and reactant concentrations are decoupled and shown to form the key independent determinants of nanoMOF sizes, thereby validating the proposal that nanoMOFs arise from coupled equilibria involving ligand deprotonation and metal-ligand complexation. By achieving the first demonstration of a seesaw relationship between nanoMOF sizes and ligand excess, these results provide further proof of the model, as they required deliberate manipulation of relationships outlined by the model. Exploring the relative impacts of these parameters reveals that ligand excess has the greatest ability to decrease sizes, although low acidity and high concentrations can exhibit similar effects. As a complement to existing models of polymer formation and crystal growth, the seesaw model therefore offers a powerful tool for reliable control over nanoMOF sizes.</p>

Experimental Evidence for a General Model of Modulated MOF Nanoparticle Growth

<p>Nanoparticles of metal-organic frameworks (nanoMOFs) boast superior properties compared to their bulk analogs, yet little is known about how common synthetic parameters dictate particle sizes. Here, we provide experimental evidence for the “seesaw” model of nanoMOF growth. Solution acidity, ligand excess, and reactant concentrations are decoupled and shown to form the key independent determinants of nanoMOF sizes, thereby validating the proposal that nanoMOFs arise from coupled equilibria involving ligand deprotonation and metal-ligand complexation. By achieving the first demonstration of a seesaw relationship between nanoMOF sizes and ligand excess, these results provide further proof of the model, as they required deliberate manipulation of relationships outlined by the model. Exploring the relative impacts of these parameters reveals that ligand excess has the greatest ability to decrease sizes, although low acidity and high concentrations can exhibit similar effects. As a complement to existing models of polymer formation and crystal growth, the seesaw model therefore offers a powerful tool for reliable control over nanoMOF sizes.</p>