The FtsZ protein, a tubulin-like GTPase, plays a pivotal role in prokaryotic cell division. In vivo it localizes to the midcell and assembles into a ring-like structure-the Z-ring. The Z-ring serves as an essential scaffold to recruit all other division proteins and generates contractile force for cytokinesis, but its supramolecular structure remains unknown. Electron microscopy (EM) has been unsuccessful in detecting the Z-ring due to the dense cytoplasm of bacterial cells, and conventional fluorescence light microscopy (FLM) has only provided images with limited spatial resolution (200–300 nm) due to the diffraction of light. Hence, given the small sizes of bacteria cells, identifying the in vivo structure of the Z-ring presents a substantial challenge. Here, we used photoactivated localization microscopy (PALM), a single molecule-based super-resolution imaging technique, to characterize the in vivo structure of the Z-ring in E. coli. We achieved a spatial resolution of ∼35 nm and discovered that in addition to the expected ring-like conformation, the Z-ring of E. coli adopts a novel compressed helical conformation with variable helical length and pitch. We measured the thickness of the Z-ring to be ∼110 nm and the packing density of FtsZ molecules inside the Z-ring to be greater than what is expected for a single-layered flat ribbon configuration. Our results strongly suggest that the Z-ring is composed of a loose bundle of FtsZ protofilaments that randomly overlap with each other in both longitudinal and radial directions of the cell. Our results provide significant insight into the spatial organization of the Z-ring and open the door for further investigations of structure-function relationships and cell cycle-dependent regulation of the Z-ring.

to ICAM-1; our results reveal that this is due to a change in the multivalency (or number of bonds formed per NC). The trend and threshold values are exactly recovered by the in vivo measurements of the endothelium targeting of NCs in the pulmonary vascular in mice [Liu et al. PNAS 107: 16530-16535 (2010)]. Increasing the shear flow rate enhances the NC binding affinities till a threshold value is reached; this quantitatively agrees with existing experiments and a novel mechanism is revealed based on our model results. On this basis, our computational protocol represents a quantitative and predictive approach for model driven design and optimization of functionalized nanocarriers in targeted vascular drug delivery.

Peer-reviewed journal publication is the main means for academic researchers in the life sciences to create a permanent public record of their work. These publications are also the de facto currency for career progress, with a strong link between journal brand recognition and perceived value. The current peer-review process can lead to long delays between submission and publication, with cycles of rejection, revision, and resubmission causing redundant peer review. This situation creates unique challenges for early career researchers (ECRs), who rely heavily on timely publication of their work to gain recognition for their efforts. Today, ECRs face a changing academic landscape, including the increased interdisciplinarity of life sciences research, expansion of the researcher population, and consequent shifts in employer and funding demands. The publication of preprints, publicly available scientific manuscripts posted on dedicated preprint servers prior to journal-managed peer review, can play a key role in addressing these ECR challenges. Preprinting benefits include rapid dissemination of academic work, open access, establishing priority or concurrence, receiving feedback, and facilitating collaborations. Although there is a growing appreciation for and adoption of preprints, a minority of all articles in life sciences and medicine are preprinted. The current low rate of preprint submissions in life sciences and ECR concerns regarding preprinting need to be addressed. We provide a perspective from an interdisciplinary group of ECRs on the value of preprints and advocate their wide adoption to advance knowledge and facilitate career development.

We study the liquid-crystalline phase behavior of a concentrated suspension of helical flagella isolated from Salmonella typhimurium. Flagella are prepared with different polymorphic states, some of which have a pronounced helical character while others assume a rodlike shape. We show that the static phase behavior and dynamics of chiral helices are very different when compared to simpler achiral hard rods. With increasing concentration, helical flagella undergo an entropy-driven first order phase transition to a liquid-crystalline state having a novel chiral symmetry. DOI: 10.1103/PhysRevLett.96.018305 PACS numbers: 82.70.ÿy, 61.30.Vx Molecules with chiral symmetry cannot be superimposed on their mirror image. Such molecules can assemble into a variety of complex chiral structures of importance to both physics and biology [1]. Chirality has a special prominence in the field of liquid crystals, and the presence of a chiral center can dramatically alter the liquid-crystalline phase behavior and its material properties [2]. For example, achiral rods form a nematic phase with long-range orientational order. However, rearranging a few atoms to create a microscopically chiral molecule can transform a nematic into a cholesteric phase. Locally, a cholesteric phase has a structure in which molecules are organized in layers. Within a layer, the molecules are parallel to each other, while the molecular orientation is slightly rotated between two adjacent layers. This order at least partially satisfies the pair interaction between neighboring chiral molecules which tends to twist their mutual orientation. Even for the fairly simple example of a cholesteric phase, it is difficult to establish a rigorous relation between the microscopic chirality of the constituent molecules and the macroscopic chirality characterized by the cholesteric pitch [3,4].In stark contrast to our poor understanding of the cholesteric phase, microscopic theories of nematic liquid crystals have been very fruitful [5]. Onsager realized that a simple fluid of concentrated hard rods will form a stable nematic phase. Using his theory, it is possible to predict the macroscopic phase behavior of a nematic suspension of hard rods from microscopic parameters such as rod concentration and rod aspect ratio. Because of the dominance of repulsive interactions, phase transitions within the Onsager model belong to a class of entropy-driven phase transitions. Inspired by the success of the Onsager theory, Straley made the first attempt at formulating a microscopic theory of the cholesteric phase [4]. In this work, hard-rod interactions are extended to threaded rods, which have an appearance similar to screws. The excluded volume between two threaded rods is at a minimum not when they are parallel to each other but when they approach each other at an angle at which their chiral grooves can interpenetrate. This results in the formation of a cholesteric phase that is, as in the Onsager model, entirely driven by entropic excluded volume interactions.Biopolymers suc...