Mapping a single-molecule folding process onto a topological space

Physics of protein folding has been dominated by conceptual frameworks including nucleation-propagation mechanism and the diffusion-collision model, none address topological properties of a chain during a folding process. Single-molecule interrogation of folded biomolecules has enabled real-time monitoring of the folding processes at an unprecedented resolution. Despite these advances, the topology landscape has not been fully mapped for any chain. Using a novel circuit topology approach, we map the topology landscape of a model polymeric chain. Inspired by single-molecule mechanical interrogation studies, we restrained the ends of a chain and followed fold nucleation dynamics. We find that, before the nucleation, transient local entropic loops dominate. Although the nucleation length of globules is dependent on the cohesive interaction, the ultimate topological states of the collapsed polymer are largely independent of the interaction but depend on the speed of the folding process. After the nucleation, transient topological rearrangements are observed that converge to a steady-state, where the fold grows in a self-similar manner

Budding and fission of nanovesicles induced by membrane adsorption of small solutes

Membrane budding and fission are essential cellular processes that produce new membrane compartments during cell and organelle division, for intracellular vesicle trafficking as well as during endo- and exocytosis. Such morphological transformations have also been observed for giant lipid vesicles with a size of many micrometers. Here, we report budding and fission processes of lipid nanovesicles with a size below 50 nm. We use coarse-grained molecular dynamics simulations, by which we can visualize the morphological transformations of individual vesicles. The budding and fission processes are induced by low concentrations of small solutes that absorb onto the outer leaflets of the vesicle membranes. In addition to the solute concentration, we identify the solvent conditions as a second key parameter for these processes. For good solvent conditions, the budding of a nanovesicle can be controlled by reducing the vesicle volume for constant solute concentration or by increasing the solute concentration for constant vesicle volume. After the budding process is completed, the budded vesicle consists of two membrane subcompartments which are connected by a closed membrane neck. The budding process is reversible as we demonstrate explicitly by reopening the closed neck. For poor solvent conditions, on the other hand, we observe two unexpected morphological transformations of nanovesicles. Close to the binodal line, at which the aqueous solution undergoes phase separation, the vesicle exhibits recurrent shape changes with closed and open membrane necks, reminiscent of flickering fusion pores (kiss-and-run) as observed for synaptic vesicles. As we approach the binodal line even closer, the recurrent shape changes are truncated by the fission of the membrane neck which leads to the division of the nanovesicle into two daughter vesicles. In this way, our simulations reveal a nanoscale mechanism for the budding and fission of nanovesicles, a mechanism that arises from the interplay between membrane elasticity and solute-mediated membrane adhesion

Effect of Zinc supplementation on serum testosterone and plasma lactate in male cyclist after one bout of exhaustive exercise

Background and aims: There is fairly scarce information about the effects of zinc, an essential trace element, on exercise performance. Studies concentrate mostly on the distribution of this element in the body in response to exercise. The purpose of this study was to investigate the effect of exhaustion exercise on the testosterone levels and plasma lactates in road cyclists who are supplemented with oral zinc for 4 weeks. Methods: In this semi experimental sixteen male road cyclists, who were healthy in the first evaluation were selected from the Tehran traffic team and were divided into two groups according to mass body index zinc group and control group. After 4 weeks zinc supplementation (30 mg/day), blood samples were collected from each subject before and after an exhaustive exercise bout. Data were analyzed by independent and paired sample t test. Results: Total testosterone, free testosterione and lactate levels in two groups were increased by exercise (P0.05). There was a significant difference between effects of exhaustion exercise on free testosterone levels between two groups (P<0.05). Conclusion: According to this study, zinc supplementation has no significant effects on testosterone and lactate levels in response to exercise in subjects with a balance diet. However, free testosterone levels were increased by exercise after zinc supplementation

Polymorphism of Biomembranes at the Nanoscale

In dieser Arbeit untersuchen wir den Polymorphismus von Biomembranen im Nanometerbereich anhand von Computermodellen. In Kapitel drei werden auf Dissipative Particle Dynamis basierende molekulare Simulationen genutzt, um die Wechselwirkungen zwischen Membranen und Nanotropfen mit hohen Oberflächenspannungen in der Größenordnung von Milli Newton pro Meter zu untersuchen. Wir zeigen, dass Nanotropfen eine negative Linienspannung an der dreiphasigen Kontaktlinie mit der Membran aufweisen. Die negative Linienspannung führt zu einem spontanen Symmetriebruch des Membran-Tropfensystems und zur Bildung eines enggeschlossenen länglichen Membranhalses. In Kapitel vier untersuchen wir Nanotropfen mit niedrigen Grenzflächenspannungen in der Größenordnung von Mikro-Newton pro Meter. Eine Energieminimierung ermöglicht uns, eine Vielzahl von Parametern zu variieren und die Abhängigkeit der Membranbenet-zungsphänomene von der Grenzflächenspannung, der Biegesteifigkeit, der Linienspannung und der spontanen Krümmung systematisch zu bestimmen. Wir beobachten eine neue morphologische Transformation, die sowohl die Vesikel als auch das Tröpfchen betrifft und eine weiter Geometrie mit gebrochener Rotationssymmetrie. Schließlich bestimmen wir die Grenze zwischen symmetrischen und asymmetrischen Kontaktlinien innerhalb des dreidimensionalen Parameterraums bei verschwindender spontanen Krümmung. In Kapitel fünf verwenden wir molekulare Simulationen, um die morphologischen Transformationen einzelner Nanovesikel mit unterschiedlichem Grad an Asymmetrie zwischen den beiden Schichten der Doppelmembranen zu beobachten. Wir beginnen mit kugelförmigen Vesikeln, die ein bestimmtes Wasservolumen einschließen und aus einer bestimmten Gesamtzahl von Lipiden bestehen. Wenn ihr Volumen verringert wird, verwandeln sich die kugelförmigen Vesikel in eine Vielzahl von nicht kugelförmigen Formen. Dieser Polymorphismus kann durch Umverteilung weniger Lipide zwischen der inneren und äußeren Schicht der Membranen kontrolliert werden.In this thesis, we use computational methods to study polymorphism of biomembranes at the nanoscales. In chapter three, we use molecular simulations based on dissipative particle dynamics to investigate the interaction of membranes with nanodroplets at high interfacial tensions of the order of milli Newton per meter. We find that nanodroplets have negative line tension at the three phase contact line on the membrane. The negative line tension leads to spontaneous symmetry breaking of the membrane-droplet system and formation of a tight-lipped membrane neck. In chapter four, we study nanodroplets with low interfacial tensions of the order of micro Newton per meter. We use energy minimization, which allows us to explore a wide range of parameters and to systemati-cally determine the dependence of membrane wetting phenomena on interfacial tension, bending rigidity, line tension, and spontaneous curvature. We observe a new morphological transformation that involves both vesicles and droplets, leads to another regime with broken rotational symmetry. Finally, we determine the boundary between symmetric and asymmetric contact line geometries within the three-dimensional parameter space in vanishing spontaneous curvature. In chapter five, we use molecular simulations to monitor the morphological transformations of individual nanovesicles with different degrees of asymmetry between the two leaflets of the bilayer membranes. We start with the assembly of spherical vesicles that enclose a certain volume of water and contain a certain total number of lipids. When we reduce their volume, the spherical vesicles transform into a multitude of nonspherical shapes such as oblates and stomatocytes as well as prolates and dumbbells. This polymorphism can be controlled by redistributing a small fraction of lipids between the inner and outer leaflets of the bilayer membranes. As a consequence, the inner and the outer leaflets experience different mechanical tensions

Mutual remodeling of interacting nanodroplets and vesicles

Biomolecular condensates are membrane-less organelles performing various functions inside cells which behaviour can be understood in terms of liquid-liquid phase separation and wetting. Here, the authors characterize the low interfacial tension regime of nanodroplets during endocytic and exocytic engulfment within an elastic membrane, study the role of the contact line symmetry, and show that nanodroplets and vesicles mutually remodel one anothe

Different pathways for engulfment and endocytosis of liquid droplets by nanovesicles

In this work, the authors investigate on how condensate droplets, arising from liquid-liquid phase separation, can be engulfed by nanovesicles via distinct pathways, leading to different vesicle-droplet morphologies. Two key parameters are the stress asymmetry of the vesicle membrane and the line tension of the contact line between vesicle and droplet

The Effect of Exercise on the Total Number of Blood Leukocytes and Platelets of the Athletes in Cold, Warm and Normal Temperature Conditions

Background & Aim: Both exercise and unusual environments cause changes in the immune system function. The aim of this study was to compare the effect of exercise on the total numbers of blood Leukocytes and platelets of the athletes in cold, warm and normal temperature conditions. Methods: In this clinical trial, ten young male endurance athletes conducted the same exercise (treadmill running) for an hour at the intensity of %60 VO2 max in three normal, cold and warm temperature conditions. The number of Leukocytes, neutrophils, lymphocytes, monocytes and platelets were counted before, immediately and two hours after exercise (during recovery). The collected data were analyzed using the repeated measure and post hoc Bonferroni tests. Results: The total number of leukocytes increased significantly after exercise, in all circumstances (p0.05). During the rest period (recovery), the number of monocytes and lymphocytes decreased significantly in cold, normal and warm environments (p< 0.05) while decreases in the number of leukocyte, exception with neutrophils, was not significant in the warm environment (p<0.05). Conclusion: Exercise in cold, normal and warm environments caused stimulation and aggregation of immune cells. However, the exercise in warm environment increased the number of blood immune cells and also delayed the immune system in reaching the initial condition during the rest period, after the exercise