Liquid-ordered lipid domains represent a lateral inhomogeneity in cellular membranes. these domains have elastic and physicochemical properties different from those of the surrounding membrane. in particular, their thickness exceeds that of the disordered membrane. thus, elastic deformations arise at the domain boundary in order to compensate for the thickness mismatch. in equilibrium, the deformations lead to an incomplete register of monolayer ordered domains: the elastic energy is minimal if domains in opposing monolayers lie on the top of each other, and their boundaries are laterally shifted by about 3 nm. This configuration introduces a region, composed of one ordered and one disordered monolayers, with an intermediate bilayer thickness. Besides, a jump in a local monolayer curvature takes place in this intermediate region, concentrating here most of the elastic stress. This region can participate in a lateral sorting of membrane inclusions by offering them an optimal bilayer thickness and local curvature conditions. In the present study, we consider the sorting of deformable lipid inclusions, undeformable peripheral and deeply incorporated peptide inclusions, and undeformable transmembrane inclusions of different molecular geometry. With rare exceptions, all types of inclusions have an affinity to the ordered domain boundary as compared to the bulk phases. the optimal lateral distribution of inclusions allows relaxing the elastic stress at the boundary of domains.Cellular membranes are laterally heterogeneous 1-3 . Many membrane proteins are believed to function properly only inside lipid-protein domains, also referred to as rafts 4-7 . Proteins in these domains are surrounded by a more or less thick lipid shell [8][9][10][11] . In model purely lipidic systems it is demonstrated that lipids can form similar domains, in which they are in a liquid-ordered (L o ) phase state, while the surrounding membrane is liquid-disordered (L d ) [12][13][14][15] . Ordered domains are usually bilayer, i.e. exist in both membrane leaflets at the same lateral position [14][15][16][17] . Such transbilayer coupling could be driven by elastic deformations arising at the domain boundary and by membrane thermal fluctuations 18-21 . The mechanism of this coupling is not specific to the exact lipid composition of the domain: only the higher ordering of lipids with respect to the surrounding membrane is important [22][23][24] . A bilayer structure of rafts is believed to be a key property in providing raft-dependent signal transduction across the plasma membrane 4,5 . There are increasing evidences that a raft interior itself may be laterally inhomogeneous: some molecules may prefer its boundary region rather than its bulk part. In particular, the fusion peptide of the human immunodeficiency virus (HIV) gp41 protein functions with the highest efficiency only in the presence of the L o /L d phase boundary in the target membrane 25,26 . In addition, the HIV receptor CCR5 preferentially localizes at the domain boundary 26 . It means t...

Sphingomyelin- and cholesterol- enriched membrane domains, commonly referred to as “rafts” play a crucial role in a large number of intra- and intercellular processes. Recent experiments suggest that not only the volumetric inhomogeneity of lipid distribution in rafts, but also the arrangement of the 1D boundary between the raft and the surrounding membrane is important for the membrane-associated processes. The reason is that the boundary preferentially recruits different peptides, such as HIV (human immunodeficiency virus) fusion peptide. In the present work, we report a theoretical investigation of mechanisms of influence of the raft boundary arrangement upon virus-induced membrane fusion. We theoretically predict that the raft boundary can act as an attractor for viral fusion peptides, which preferentially distribute into the vicinity of the boundary, playing the role of ‘line active components’ of the membrane (‘linactants’). We have calculated the height of the fusion energy barrier and demonstrated that, in the case of fusion between HIV membrane and the target cell, presence of the raft boundary in the vicinity of the fusion site facilitates fusion. The results we obtained can be further generalized to be applicable to other enveloped viruses.

Аннотация В данной статье рассмотрен один из видов координационных способностей, необходимых танцору для проявления технического мастерства при выполнении соревновательной программы: способности поддерживать статическое (позу) и динамическое равновесие. Для оценки данного вида координационных способностей взята методика Биодекс-баланс, позволяющая оценить следующие показатели: постуральную устойчивость-способность поддерживать вертикальное положение тела, что сопряжено со способностью поддержания центра давления тела внутри границ площади опоры и лимит стабильности-определяющий максимальное расстояние, которое человек может намеренно смещать центр тяжести. В результате исследования были разработаны параметры тестирования и шкалы оценки статического и динамического равновесия для спортсменовтанцоров. Ключевые слова: спортивные бальные танцы, координационные способности, статическое и динамическое равновесие, постуральная устойчивость, лимит стабильности.

Despite an extensive literature on statistical methods and their proper application to biological data, incorrect analyses remain a critical and widely spread problem in research papers. Inherently hierarchical (nested, clustered) structure of biological measurements is often erroneously neglected, leading to pseudo-replication and false positive results. This, in turn, complicates the correct assessment of statistical power and impairs optimal planning of experiments. In order to attract more attention to this problem and to illustrate the importance of direct account for the nested structure of biological data, in this article we present a simple open-source simulator of two-level normally distributed stochastic data. By defining 'true' mean values and 'true' intraand inter-cluster variances of the simulated data, users of the simulator can test various scenarios, appreciate the importance of using correct multi-level analysis and the danger of neglecting the information about the data structure. Here we apply our nested data simulator to highlight some commonly arising mistakes with data analysis and propose a workflow, in which our simulator could be employed to correctly compare two nested groups of experimental data and to optimally plan new experiments in order to increase statistical power when necessary.

Microtubules are essential cytoskeletal polymers that exhibit stochastic switches between tubulin assembly and disassembly. Here, we examine possible mechanisms for these switches, called catastrophes and rescues. We formulate a four-state Monte Carlo model, explicitly considering two biochemical and two conformational states of tubulin, based on a recently conceived view of microtubule assembly with flared ends. The model predicts that high activation energy barriers for lateral tubulin interactions can cause lagging of curled protofilaments, leading to a ragged appearance of the growing tip. Changes in the extent of tip raggedness explain some important but poorly understood features of microtubule catastrophe: weak dependence on tubulin concentration and an increase in its probability over time, known as aging. The model predicts a vanishingly rare frequency of spontaneous rescue unless patches of guanosine triphosphate tubulin are artificially embedded into microtubule lattice. To test our model, we used in vitro reconstitution, designed to minimize artifacts induced by microtubule interaction with nearby surfaces. Microtubules were assembled from seeds overhanging from microfabricated pedestals and thus well separated from the coverslip. This geometry reduced the rescue frequency and the incorporation of tubulins into the microtubule shaft compared with the conventional assay, producing data consistent with the model. Moreover, the rescue positions of microtubules nucleated from coverslip-immobilized seeds displayed a nonexponential distribution, confirming that coverslips can affect microtubule dynamics. Overall, our study establishes a unified theory accounting for microtubule assembly with flared ends, a tip structure–dependent catastrophe frequency, and a microtubule rescue frequency dependent on lattice damage and repair.