Transient pores in hemifusion diaphragms.

Exchange of material across two membranes, as in the case of synaptic neurotransmitter release from a vesicle, involves the formation and poration of a hemifusion diaphragm (HD). The nontrivial geometry of the HD leads to environment-dependent control, regarding the stability and dynamics of the pores required for this kind of exocytosis. This work combines particle simulations, field-based calculations, and phenomenological modeling to explore the factors influencing the stability, dynamics, and possible control mechanisms of pores in HDs. We find that pores preferentially form at the HD rim, and that their stability is sensitive to a number of factors, including the three line tensions, membrane tension, HD size, and the ability of lipids to "flip-flop" across leaflets. Along with a detailed analysis of these factors, we discuss ways that vesicles or cells may use them to open and close pores and thereby quickly and efficiently transport material.

Membrane fission via transmembrane contact.

Division of intracellular organelles often correlates with additional membrane wrapping, e.g., by the endoplasmic reticulum or the outer mitochondrial membrane. Such wrapping plays a vital role in proteome and lipidome organization. However, how an extra membrane impacts the mechanics of the division has not been investigated. Here we combine fluorescence and cryo-electron microscopy experiments with self-consistent field theory to explore the stress-induced instabilities imposed by membrane wrapping in a simple double-membrane tubular system. We find that, at physiologically relevant conditions, the outer membrane facilitates an alternative pathway for the inner-tube fission through the formation of a transient contact (hemi-fusion) between both membranes. A detailed molecular theory of the fission pathways in the double membrane system reveals the topological complexity of the process, resulting both in leaky and leakless intermediates, with energies and topologies predicting physiological events.

Interplay between nematic and cholesteric interactions in self-consistent field theory.

Chirality is a design feature of a number of biomolecules (e.g., collagen). In these molecules, cholesteric (chiral-nematic) behavior emerges from a combination of the tendency for the biopolymers to align (nematic interactions) and for the alignment direction to change with position, rotating around an axis normal to the alignment direction. This paper presents self-consistent field theory (SCFT) of chiral-nematic polymers, which takes into account polymer flexibility and the orientational degrees of freedom of polymer segments. Using the resulting SCFT, we construct a phase diagram showing regions of stability for isotropic, nematic, and cholesteric phases. Furthermore, we find that nematic interactions can stabilize the cholesteric phase, pushing the isotropic-cholesteric phase transition to lower cholesteric interaction strength, until the isotropic-nematic-cholesteric triple point is reached.

Self-consistent field theory of chiral nematic worm-like chains.

Many macromolecules of biological and technological interest are both chiral and semi-flexible. DNA and collagen are good examples. Such molecules often form chiral nematic (or cholesteric) phases, as is well-documented in collagen and chitin. This work presents a method for studying cholesteric phases in the highly successful self-consistent field theory of worm-like chains, offering a new way of studying many biologically relevant molecules. The method involves an effective Hamiltonian with a chiral term inspired by the Oseen-Frank (OF) model of liquid crystals. This method is then used to examine the formation of cholesteric phases in chiral-nematic worm-like chains as a function of polymer flexibility, as well as the optimal cholesteric pitch and distribution of polymer segment orientations. Our approach not only allows for the determination of the isotropic-cholesteric transition and segment distributions, beyond what the OF model promises, but also explicitly incorporates polymer flexibility into the study of the cholesteric phase, offering a more complete understanding of the behavior of semiflexible chiral-nematic polymers.

Instability of the Microemulsion Channel in Block Copolymer-Homopolymer Blends.

Field theoretic simulations are used to predict the equilibrium phase diagram of symmetric blends of AB diblock copolymer with A- and B-type homopolymers. Experiments generally observe a channel of bicontinuous microemulsion (BµE) separating the ordered lamellar (LAM) phase from coexisting homopolymer-rich (A+B) phases. However, our simulations find that the channel is unstable with respect to macrophase separation, in particular, A+B+BµE coexistence at high T and A+B+LAM coexistence at low T. The preference for three-phase coexistence is attributed to a weak attractive interaction between diblock monolayers.

Nematic ordering of worm-like polymers near an interface.

The phase behavior of semi-flexible polymers is integral to various contexts, from materials science to biophysics, many of which utilize or require specific confinement geometries as well as the orientational behavior of the polymers. Inspired by collagen assembly, we study the orientational ordering of semi-flexible polymers, modeled as Maier-Saupe worm-like chains, using self-consistent field theory. We first examine the bulk behavior of these polymers, locating the isotropic-nematic transition and delineating the limit of stability of the isotropic and nematic phases. This effort explains how nematic ordering emerges from the isotropic phase and offers insight into how different (e.g., mono-domain vs multi-domain) nematic phases form. We then clarify the influence of planar confinement on the nematic ordering of the polymers. We find that while the presence of a single confining wall does not shift the location of nematic transition, it aligns the polymers in parallel to the wall; above the onset of nematic transition, this preference tends to propagate into the bulk phase. Introducing a second, perpendicular, wall leads to a nematic phase that is parallel to both walls, allowing the ordering direction to be uniquely set by the geometry of the experimental setup. The advantage of wall-confinement is that it can be used to propagate mono-domain nematic phases into the bulk phase.

Field-theoretic simulations of bottlebrush copolymers.

Traditional particle-based simulations struggle with large bottlebrush copolymers, consisting of many side chains grafted to a backbone. Field-theoretical simulations (FTS) allow us to overcome the computational demands in order to calculate their equilibrium behavior. We consider bottlebrushes where all grafts are symmetric diblock copolymers, focusing on the order-disorder transition (ODT) and the size of ordered domains. Increasing the number of grafts and decreasing the spacing between them both raise the transition temperature. The ODT and lamellar period asymptotically approach constants as the number of grafts increases. As the spacing between grafts becomes large, the bottlebrushes behave like diblock copolymers, and as it becomes small, they behave like starblock copolymers. In between, the period increases, reaching a maximum when the spacing is approximately 0.35 times the length of the grafts. A comparison of FTS with mean-field calculations allows us to assess the effect of compositional fluctuations. Fluctuations suppress ordering, while having little effect on the period, as is the case for diblock copolymers.

Fluctuation effects in blends of A + B homopolymers with AB diblock copolymer.

Field-theoretic simulations (FTSs) are performed on ternary blends of A- and B-type homopolymers of polymerization Nh and symmetric AB diblock copolymers of polymerization Nc. Unlike previous studies, our FTSs are conducted in three-dimensional space, with the help of two new semi-grand canonical ensembles. Motivated by the first experiment to discover bicontinuous microemulsion (BµE) in the polyethylene-polyethylene propylene system, we consider molecules of high molecular weight with size ratios of α ≡ Nh/Nc = 0.1, 0.2, and 0.4. Our focus is on the A + B coexistence between the two homopolymer-rich phases in the low-copolymer region of the phase diagram. The Scott line, at which the A + B phases mix to form a disordered melt with increasing temperature (or decreasing χ), is accurately determined using finite-size scaling techniques. We also examine how the copolymer affects the interface between the A + B phases, reducing the interfacial tension toward zero. Although comparisons with self-consistent field theory (SCFT) illustrate that fluctuation effects are relatively small, fluctuations do nevertheless produce the observed BµE that is absent in the SCFT phase diagram. Furthermore, we find evidence of three-phase A + B + BµE coexistence, which may have been missed in the original as well as subsequent experiments.

Manipulating the ABCs of self-assembly via low-χ block polymer design.

Block polymer self-assembly typically translates molecular chain connectivity into mesoscale structure by exploiting incompatible blocks with large interaction parameters (χij). In this article, we demonstrate that the converse approach, encoding low-χ interactions in ABC bottlebrush triblock terpolymers (χAC [Formula: see text] 0), promotes organization into a unique mixed-domain lamellar morphology, which we designate LAMP Transmission electron microscopy indicates that LAMP exhibits ACBC domain connectivity, in contrast to conventional three-domain lamellae (LAM3) with ABCB periods. Complementary small-angle X-ray scattering experiments reveal a strongly decreasing domain spacing with increasing total molar mass. Self-consistent field theory reinforces these observations and predicts that LAMP is thermodynamically stable below a critical χAC, above which LAM3 emerges. Both experiments and theory expose close analogies to ABA' triblock copolymer phase behavior, collectively suggesting that low-χ interactions between chemically similar or distinct blocks intimately influence self-assembly. These conclusions provide fresh opportunities for block polymer design with potential consequences spanning all self-assembling soft materials.

Nucleation of the BCC phase from disorder in a diblock copolymer melt: Testing approximate theories through simulation.

We examine nucleation of the stable body-centred-cubic (BCC) phase from the metastable uniform disordered phase in an asymmetric diblock copolymer melt. Our comprehensive, large-scale simulations of the time-dependent, mean-field Landau-Brazovskii model find that spherical droplets of the BCC phase nucleate directly from disorder. Near the order-disorder transition, the critical nucleus is large and has a classical profile, attaining the bulk BCC phase in an interior that is separated from disorder by a sharp interface. At greater undercooling, the amplitude of BCC order in the interior decreases and the nucleus interface broadens, leading to a diffuse critical nucleus. This diffuse nucleus becomes large as the simulation approaches the disordered phase spinodal. We show that our simulation follows the same nucleation pathway that Cahn and Hilliard found for an incompressible two-component fluid, across the entire metastable region. In contrast, a classical nucleation theory calculation based on the free energy of a planar interface between coexisting BCC and disordered phases agrees with simulation only in the limit of very small undercooling; we can expand this region of validity somewhat by accounting for the curvature of the droplet interface. A nucleation pathway involving a classical droplet persists, however, to deep undercooling in our simulation, but this pathway is energetically unfavourable. As a droplet grows in the simulation, its interface moves with a constant speed, and this speed is approximately proportional to the undercooling.

Confinement effects on the miscibility of block copolymer blends.

Thin films of long and short symmetric AB diblock copolymers are examined using self-consistent field theory (SCFT). We focus on hard confining walls with a preference for the A component, such that the lamellar domains orient parallel to the film with an even number ν of monolayers. For neat melts, confinement causes the lamellar period, D, to deviate from its bulk value, Db, in order to be commensurate with the film thickness, i.e., L = νD/2. For blends, however, the melt also has the option of macrophase separating into ν(l) large and ν((s)) small monolayers so as to provide a better fit, where L = ν(l)D(l)/2 + ν(s)D((s))/2. In addition to performing full SCFT calculations of the entire film, we develop a semi-analytical calculation for the coexistence of thick and thin monolayers that helps explain the complicated interplay between miscibility and commensurability.

Non-operative treatment versus percutaneous drainage of pancreatic pseudocysts in children.

PURPOSE: The objective of this study was to characterize the clinical course and outcomes of children with pancreatic pseudocysts that were initially treated non-operatively or with percutaneous drainage. METHODS: A retrospective review of children with pancreatic pseudocysts over a 12-year period was completed. Categorical variables were compared using Fischer's exact method and the Student's t test was used to compare continuous variables. Analysis was done using logistic and linear regression models. RESULTS: Thirty-six children met the criteria for pancreatic pseudocyst and 33 children were treated either non-operatively or with percutaneous drainage. Of the 22 children managed non-operatively, 17 required no additional intervention (77 %) and five required surgery. Operative procedures were: Frey procedure (3), distal pancreatectomy (1), and cystgastrostomy (1). Eight of the 11 children treated with initial percutaneous drainage required no additional treatment (72 %). The other three children underwent distal pancreatectomy. Success of non-operative management or percutaneous drainage was not dependent on size or complexity of the pseudocyst Logistic regression did not identify any patient demographic (gender, age, and weight), etiologic (trauma, non-traumatic pancreatitis) or pseudocyst characteristic (size, septations) that predicted failure of non-operative therapy. CONCLUSIONS: In children, pancreatic pseudocysts can frequently be managed without surgery regardless of size or complexity of the pseudocyst. When an intervention is needed, percutaneous drainage can be performed successfully, avoiding the need for major surgical intervention in the majority of patients.

Removing swing from a handstand on rings using a properly timed backward giant circle: a simulation solution.

In the rings event in men's gymnastics, marks are deducted if the rings and gymnast are swinging during a held handstand position. The unwanted swing can be reduced in the next handstand position if the gymnast is able to properly time the start of the connecting giant circle. The purpose of this study was to search for the optimal time to commence a backward giant circle in order to attenuate swing in the succeeding handstand. Computer simulations, using a four-segment and a three-segment model which employed two-pulse muscular control strategies, were used to search for the optimal timing solution. Qualitative validation tests between the performance of a world class gymnast and the simulation models indicated that a three-segment model comprising a cables-rings segment, an arms segment with a shoulder torque generator, and a head-torso-legs segment, produced similar results to that of a four-segment model which separated the legs segment from the torso and employed an additional torque generator at the hip joint. The results from the simulation indicated that a gymnast should be advised to initiate a backward giant circle when his swinging handstand has reached the bottom of its swing-arc. For a handstand with an original swing-amplitude of 10 degrees, the simulation results indicate that a properly timed backward giant circle can reduce this amplitude to a negligible 1.5 degrees of swing.

Knee muscle strength in elite male gymnasts.

This study was launched to establish the profile of knee dynamic concentric strength in elite male gymnasts after it was found that three of the 10-member Canadian men's gymnastics team had incurred anterior cruciate ligament (ACL) rupture. The dynamic concentric force characteristics of the quadriceps and hamstring muscles of 84 male gymnasts were studied at the Canadian National Championships using a Kin-Com isokinetic dynamometer. These tests were performed at 90 degrees/sec and 230 degrees/sec and revealed that the hamstrings to quadriceps peak torque ratio was not only unusually low (0.5) when compared with data collected in previous research, but that this ratio was consistent across all ages, from 12 to 27 years. The torque ratios were also reported at 30 degrees, 45 degrees, and 60 degrees and it was found that the ratios decreased as the joint angle increased and again was consistent across the four age groups. It was also found that the hamstrings to quadriceps peak torque ratio did not increase (hamstrings becoming stronger relative to quadriceps) as velocity of movement increased as has been reported in other studies. It was hypothesized that the large shear forces that are generated about the knee in gymnastics (extrinsically from backward landing and intrinsically from the quadriceps eccentrically contracting), combined with the relatively weak hamstrings, could be one cause for the increasing incidence of ACL injuries in that sport. The results of this study indicate that it would be prudent for clinicians involved with gymnasts to test for knee strength imbalance and to prescribe exercises to correct it when necessary.