The field theory of symmetrical layered electrolytic systems and the thermal Casimir effect

We present a general extension of a field-theoretic approach developed in earlier papers to the calculation of the free energy of symmetrically layered electrolytic systems which is based on the Sine-Gordon field theory for the Coulomb gas. The method is to construct the partition function in terms of the Feynman evolution kernel in the Euclidean time variable associated with the coordinate normal to the surfaces defining the layered structure. The theory is applicable to cylindrical systems and its development is motivated by the possibility that a static van der Waals or thermal Casimir force could provide an attractive force stabilising a dielectric tube formed from a lipid bilayer, an example of which are t-tubules occurring in certain muscle cells. In this context, we apply the theory to the calculation of the thermal Casimir effect for a dielectric tube of radius $R$ and thickness $\delta$ formed from such a membrane in water. In a grand canonical approach we find that the leading contribution to the Casimir energy behaves like $-k_BTL\kappa_C/R$ which gives rise to an attractive force which tends to contract the tube radius. We find that $\kappa_C \sim 0.3$ for the case of typical lipid membrane t-tubules. We conclude that except in the case of a very soft membrane this force is insufficient to stabilise such tubes against the bending stress which tend to increase the radius. We briefly discuss the role of lipid membrane reservoir implicit in the approach and whether its nature in biological systems may possibly lead to a stabilising mechanism for such lipid tubes.Comment: 28 pages, 2 figures, LaTe

Effective Area-Elasticity and Tension of Micro-manipulated Membranes

We evaluate the effective Hamiltonian governing, at the optically resolved scale, the elastic properties of micro-manipulated membranes. We identify floppy, entropic-tense and stretched-tense regimes, representing different behaviors of the effective area-elasticity of the membrane. The corresponding effective tension depends on the microscopic parameters (total area, bending rigidity) and on the optically visible area, which is controlled by the imposed external constraints. We successfully compare our predictions with recent data on micropipette experiments.Comment: To be published in Phys. Rev. Let

Interactions between proteins bound to biomembranes

We study a physical model for the interaction between general inclusions bound to fluid membranes that possess finite tension, as well as the usual bending rigidity. We are motivated by an interest in proteins bound to cell membranes that apply forces to these membranes, due to either entropic or direct chemical interactions. We find an exact analytic solution for the repulsive interaction between two similar circularly symmetric inclusions. This repulsion extends over length scales of order tens of nanometers, and contrasts with the membrane-mediated contact attraction for similar inclusions on tensionless membranes. For non circularly symmetric inclusions we study the small, algebraically long-ranged, attractive contribution to the force that arises. We discuss the relevance of our results to biological phenomena, such as the budding of caveolae from cell membranes and the striations that are observed on their coats.Comment: 22 pages, 2 figure

Caspase-8 binding to cardiolipin in giant unilamellar vesicles provides a functional docking platform for bid

Caspase-8 is involved in death receptor-mediated apoptosis in type II cells, the proapoptotic programme of which is triggered by truncated Bid. Indeed, caspase-8 and Bid are the known intermediates of this signalling pathway. Cardiolipin has been shown to provide an anchor and an essential activating platform for caspase-8 at the mitochondrial membrane surface. Destabilisation of this platform alters receptor-mediated apoptosis in diseases such as Barth Syndrome, which is characterised by the presence of immature cardiolipin which does not allow caspase-8 binding. We used a simplified in vitro system that mimics contact sites and/or cardiolipin-enriched microdomains at the outer mitochondrial surface in which the platform consisting of caspase-8, Bid and cardiolipin was reconstituted in giant unilamellar vesicles. We analysed these vesicles by flow cytometry and confirm previous results that demonstrate the requirement for intact mature cardiolipin for caspase-8 activation and Bid binding and cleavage. We also used confocal microscopy to visualise the rupture of the vesicles and their revesiculation at smaller sizes due to alteration of the curvature following caspase-8 and Bid binding. Biophysical approaches, including Laurdan fluorescence and rupture/tension measurements, were used to determine the ability of these three components (cardiolipin, caspase-8 and Bid) to fulfil the minimal requirements for the formation and function of the platform at the mitochondrial membrane. Our results shed light on the active functional role of cardiolipin, bridging the gap between death receptors and mitochondria

A lattice model for the kinetics of rupture of fluid bilayer membranes

We have constructed a model for the kinetics of rupture of membranes under tension, applying physical principles relevant to lipid bilayers held together by hydrophobic interactions. The membrane is characterized by the bulk compressibility (for expansion), the thickness of the hydrophobic part of the bilayer, the hydrophobicity and a parameter characterizing the tail rigidity of the lipids. The model is a lattice model which incorporates strain relaxation, and considers the nucleation of pores at constant area, constant temperature, and constant particle number. The particle number is conserved by allowing multiple occupancy of the sites. An equilibrium ``phase diagram'' is constructed as a function of temperature and strain with the total pore surface and distribution as the order parameters. A first order rupture line is found with increasing tension, and a continuous increase in proto-pore concentration with rising temperature till instability. The model explains current results on saturated and unsaturated PC lipid bilayers and thicker artificial bilayers made of diblock copolymers. Pore size distributions are presented for various values of area expansion and temperature, and the fractal dimension of the pore edge is evaluated.Comment: 15 pages, 8 figure

Fluid-membrane tethers: minimal surfaces and elastic boundary layers

Thin cylindrical tethers are common lipid bilayer membrane structures, arising in situations ranging from micromanipulation experiments on artificial vesicles to the dynamic structure of the Golgi apparatus. We study the shape and formation of a tether in terms of the classical soap-film problem, which is applied to the case of a membrane disk under tension subject to a point force. A tether forms from the elastic boundary layer near the point of application of the force, for sufficiently large displacement. Analytic results for various aspects of the membrane shape are given.Comment: 12 page

Membranes by the Numbers

Many of the most important processes in cells take place on and across membranes. With the rise of an impressive array of powerful quantitative methods for characterizing these membranes, it is an opportune time to reflect on the structure and function of membranes from the point of view of biological numeracy. To that end, in this article, I review the quantitative parameters that characterize the mechanical, electrical and transport properties of membranes and carry out a number of corresponding order of magnitude estimates that help us understand the values of those parameters.Comment: 27 pages, 12 figure

Left ventricular false tendons: echocardiographic characteristics in the Polish population

Background: False tendon (FT) is described in a wide range (40% to 62%) of the examined hearts depending on age and additional heart abnormalities. On echocardiography, the range is even wider (1.6–78%), depending on study design and inclusion criteria. Ultrasonographic characteristics of left ventricular FTs in the Polish population are not well known. Materials and methods: Echocardiographic examinations of 1,679 consecutive patients were evaluated. All cases were classified according to American Society of Echocardiography Committee of Nomenclature and Standards Document on Identification of the Segments of the Heart Muscle. Results: In our study, fibrous structures in the lumen of the left ventricle were detected in 100 (6%) subjects of the study group. The age of the subjects ranged from 16 to 87 years (mean age 47.9), 50 were males and 50 were females. In 94% of the subjects, FT was a single structure. No patient had clinically evident arrhythmia. Conclusions: In the Polish population, FT can be identified in all age groups, and the prevalence is similar to that reported in the literature

MalnutritiOn assessment with biOelectrical impedaNce analysis in gastRic cancer patIentS undergoing multimodaltrEatment (MOONRISE)—Study protocol for a single-arm multicenter cross-sectional longitudinal study

European data suggests that over 30% of gastric cancer (GC) patients are diagnosed with sarcopenia before surgery, while unintentional weight loss occurs in approximately 30% of patients following gastrectomy. Preoperative sarcopenia significantly increases the risk of major postoperative complications, and preoperative body weight loss remains a superior predictor of outcome and an independent prognostic factor for overall survival (OS) in patients with GC. A standardized approach of nutritional risk screening of GC patients is yet to be established. Therefore, the MOONRISE study aims to prospectively analyze the changes in nutritional status and body composition at each stage of multimodal treatment among GC patients from five Western expert centers. Specifically, we seek to assess the association between nutritional status and body composition on tumor response following neoadjuvant chemotherapy (NAC). Secondary outcomes of the study are treatment toxicity, postoperative complications, quality of life (QoL), and OS. Patients with locally advanced gastric adenocarcinoma scheduled for multimodal treatment will be included in the study. Four consecutive nutritional status assessments will be performed throughout the treatment. The following study was registered in ClinicalTrials.gov (Identifier: NCT05723718) and will be conducted in accordance with the STROBE statement. The anticipated duration of the study is 12–24 months, depending on the recruitment status. Results of this study will reveal whether nutritional status and body composition assessment based on BIA will become a validated and objective tool to support clinical decisions in GC patients undergoing multimodal treatment.</p

Surgical treatment of rectal cancer in Poland — a report from a prospective, multi-centre observational study PSSO_01 conducted under the auspices of the Polish Society of Surgical Oncology

Introduction. Since 2016, as part of the PSSO_01 multi-centre research project conducted under the auspices of the Polish Society of Surgical Oncology, clinical data on rectal cancer treatment have been collected. The objective of the study was to illustrate the state of early results of surgical treatment. Material and methods. The research project is multi-centre in nature. Data shall be collected electronically. The study protocol does not impose or suggest any course of procedure. It only systematizes the way data are collected for scientific purposes. The analysis of early results of surgical treatment was compared with the results of population studies from other European countries (Netherlands, Belgium). Results. By the end of June 2018, 736 patients were registered in the study. In 399 (54.2%) an anterior resection was performed. More than half of patients undergoing subsequent surgical treatment (54.2%) receive neoadjuvant treatment, with the percentage of patients undergoing radiotherapy or radiochemical treatment for lower rectal cancer being about 70%. Most patients (96%) are operated in elective procedure. The percentage of laparoscopic surgeries is low (8.6%). Postoperative complications are observed in 21.1% of patients. Severe complications (grades III–V according to Clavien-Dindo classification) occur in 7.6% of patients undergoing surgery. Postoperative mortality is 1.1%. Discussion. Although the project does not have the character of a registry and does not allow for drawing wider conclusions concerning the compliance with the standards of qualification for neoadjuvant treatment, the important information is that more than half of rectal cancer patients receive preoperative treatment, and the percentage of severe postoperative complications does not exceed 10%. Conclusions. The results of the PSSO_01 project are representative and reflect the actual situation concerning surgical treatment of rectal cancer patients in Poland