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S. Das

Bio: S. Das is an academic researcher from Indian Institute of Technology Kanpur. The author has contributed to research in topics: Curvature & Vesicle. The author has an hindex of 14, co-authored 35 publications receiving 1142 citations. Previous affiliations of S. Das include University of Leicester & Cornell University.

Papers
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Journal ArticleDOI
TL;DR: The estimate of the principal intrinsic curvature of the protein KvAP, obtained by comparing the experimental and theoretical sorting behavior, is consistent with the available information on its structure.
Abstract: Cell membrane proteins, both bound and integral, are known to preferentially accumulate at membrane locations with curvatures favorable to their shape. This is mainly due to the curvature dependent interaction between membrane proteins and their lipid environment. Here, we analyze the effects of the protein–lipid bilayer interaction energy due to mismatch between the protein shape and the principal curvatures of the surrounding bilayer. The role of different macroscopic parameters that define the interaction energy term is elucidated in relation to recent experiment in which the lateral distribution of a membrane embedded protein potassium channel KvAP is measured on a giant unilamellar lipid vesicle (reservoir) and a narrow tubular extension – a tether – kept at constant length. The dependence of the sorting ratio, defined as the ratio between the areal density of the protein on the tether and on the vesicle, on the inverse tether radius is influenced by the strength of the interaction, the intrinsic shape of the membrane embedded protein, and its abundance in the reservoir. It is described how the values of these constants can be extracted from experiments. The intrinsic principal curvatures of a protein are related to the tether radius at which the sorting ratio attains its maximum value. The estimate of the principal intrinsic curvature of the protein KvAP, obtained by comparing the experimental and theoretical sorting behavior, is consistent with the available information on its structure.

23 citations

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TL;DR: Severe alcoholic hepatitis patients have high mortality and limited response to corticosteroids, and microvesicles reflect cellular stress and disease conditions.
Abstract: BACKGROUND Severe alcoholic hepatitis patients have high mortality and limited response to corticosteroids. Microvesicles reflect cellular stress and disease conditions. AIMS To investigate whether microvesicles are associated with severity, response to steroid therapy and inflammation in severe alcoholic hepatitis. METHODS Microvesicles originating from different cells were studied pre-therapy in 101 patients; (71 responder to corticosteroid therapy and 30 nonresponders) and 20 healthy controls. Microvesicles and cells were determined in peripheral and hepatic vein samples using flow cytometry and correlated with outcomes. Inflammatory signalling pathways and functional alterations of immune cells after stimulation with microvesicles were also investigated. RESULTS Microvesicles mean levels were higher in nonresponders for T cells (CD3+ CD4+ ; 10.1 MV/μL vs 5.4; P = 0.06), macrophages (CD68+ CD11b+ ; 136.5 vs 121.9 MV/μL; P = 0.01), haematopoietic stem-cells (CD45+ CD34+ ; 116.8 vs 13.4 MV/μL; P = 0.0001) and hepatocytes (ASGPR+ ; 470 vs 361 MV/μL; P = 0.01); the latter two predicting steroid nonresponse in 94% patients at baseline in peripheral plasma. Microvesicle levels correlated with histological and liver disease severity indices. Whereas, in non-responders hepatic vein CD34+ cells were lower (P = 0.02), the CD34+ microvesicles there from were higher (P = 0.04), thus suggesting impaired regeneration. Also, microvesicles of 0.2-0.4 μm size were higher in nonresponders (P < 0.03) at baseline. Microvesicles from patients trigger more (P = 0.04) ROS generation, TNF-α production (P = 0.04) and up-regulate pro-inflammatory cytokine related genes in neutrophils in vitro. CONCLUSIONS Pre-therapy peripheral plasma levels of CD34+ and ASGPR+ microvesicles are reliable non-invasive markers of steroid nonresponse and mortality in patients with severe alcoholic hepatitis.

20 citations

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TL;DR: In this paper, the authors provide an overview of major classes of membrane proteins and the mechanisms of curvature sensing and induction, and discuss the importance of membrane elastic characteristics to induce the membrane shapes similar to intracellular organelles.

19 citations

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TL;DR: In this paper, the authors revisited the simplest walker studied earlier by Garcia and co-workers and extended the small-slope stability analysis to second order, substantially improving accuracy, and also provided some details left out of the earlier work.
Abstract: We revisit the simplest walker studied earlier by Garcia and co-workers. We extend the small-slope stability analysis to second order, substantially improving accuracy, and also provide some details left out of the earlier work. We develop an alternative (reverse) approach for the stability analysis, which involves shorter calculations: for stability analysis upto any given order, the new procedure requires calculations to one order less than the previous (forward) procedure. The stability results obtained by the two methods arc, nevertheless, equivalent.

19 citations

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TL;DR: In this paper, Galerkin projections are used to obtain approximate realizations of the method of multiple scales and the related method of averaging are commonly used to study slowly modulated oscillations.
Abstract: The method of multiple scales and the related method of averaging are commonly used to study slowly modulated oscillations. If the system of interest is a slightly perturbed harmonic oscillator, then these techniques can be applied easily. If the unperturbed system is strongly nonlinear (though possibly conservative), then these methods can run into difficulties due to the impossibility of carrying out required analytical operations in closed form. In this paper, we abandon the requirement of closed form analytical treatment at all stages. Instead, Galerkin projections are used to obtain approximate realizations of the method of multiple scales. This paper adapts recent work using similar ideas for approximate realizations of the method of averaging. A key contribution of the present work is in the systematic identification and removal of secular terms in the general nonlinear case, a procedure that is more difficult than for the perturbed harmonic oscillator case, and that is unnecessary for averaging. A strength of the present work is that the heuristics (Galerkin) and asymptotics (multiple scales) are kept distinct, leaving room for systematic refinement of the former without compromising the asymptotic features of the latter.

17 citations


Cited by
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TL;DR: Understanding of the mechanisms by which dynamin acts, its essential roles in cell physiology and the specific function of different dynamin isoforms are improved, highlighting specific contributions of this GTPase to the physiology of different tissues.
Abstract: Dynamin, the founding member of a family of dynamin-like proteins (DLPs) implicated in membrane remodelling, has a critical role in endocytic membrane fission events. The use of complementary approaches, including live-cell imaging, cell-free studies, X-ray crystallography and genetic studies in mice, has greatly advanced our understanding of the mechanisms by which dynamin acts, its essential roles in cell physiology and the specific function of different dynamin isoforms. In addition, several connections between dynamin and human disease have also emerged, highlighting specific contributions of this GTPase to the physiology of different tissues.

829 citations

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TL;DR: It is demonstrated that giant plasma membrane vesicles (GPMVs) or blebs formed from the plasma membranes of cultured mammalian cells can also segregate into micrometer-scale fluid phase domains, and GPMVs now provide an effective approach to characterize biological membrane heterogeneities.
Abstract: The membrane raft hypothesis postulates the existence of lipid bilayer membrane heterogeneities, or domains, supposed to be important for cellular function, including lateral sorting, signaling, and trafficking. Characterization of membrane lipid heterogeneities in live cells has been challenging in part because inhomogeneity has not usually been definable by optical microscopy. Model membrane systems, including giant unilamellar vesicles, allow optical fluorescence discrimination of coexisting lipid phase types, but thus far have focused on coexisting optically resolvable fluid phases in simple lipid mixtures. Here we demonstrate that giant plasma membrane vesicles (GPMVs) or blebs formed from the plasma membranes of cultured mammalian cells can also segregate into micrometer-scale fluid phase domains. Phase segregation temperatures are widely spread, with the vast majority of GPMVs found to form optically resolvable domains only at temperatures below ≈25°C. At 37°C, these GPMV membranes are almost exclusively optically homogenous. At room temperature, we find diagnostic lipid phase fluorophore partitioning preferences in GPMVs analogous to the partitioning behavior now established in model membrane systems with liquid-ordered and liquid-disordered fluid phase coexistence. We image these GPMVs for direct visual characterization of protein partitioning between coexisting liquid-ordered-like and liquid-disordered-like membrane phases in the absence of detergent perturbation. For example, we find that the transmembrane IgE receptor FceRI preferentially segregates into liquid-disordered-like phases, and we report the partitioning of additional well known membrane associated proteins. Thus, GPMVs now provide an effective approach to characterize biological membrane heterogeneities.

780 citations

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TL;DR: In updated versions of the model more emphasis has been placed on the mosaic nature of the macrostructure of cellular membranes where many protein and lipid components are limited in their rotational and lateral motilities in the membrane plane, especially in their natural states.

546 citations

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TL;DR: A third general mechanism for bending fluid cellular membranes: protein–protein crowding is proposed, and it is found that even proteins unrelated to membrane curvature, such as green fluorescent protein (GFP), can bend membranes when sufficiently concentrated.
Abstract: Membrane deformation is necessary to generate endocytic vesicles, but the molecular mechanisms proposed to drive membrane bending are controversial. Stachowiak and Schmid et al. report that crowding of proteins at the membrane is sufficient to induce curvature in vitro.

476 citations

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TL;DR: The state of the art in the field of realistic membrane simulations is reviewed and the current limitations and challenges ahead are discussed.
Abstract: Cell membranes contain a large variety of lipid types and are crowded with proteins, endowing them with the plasticity needed to fulfill their key roles in cell functioning. The compositional complexity of cellular membranes gives rise to a heterogeneous lateral organization, which is still poorly understood. Computational models, in particular molecular dynamics simulations and related techniques, have provided important insight into the organizational principles of cell membranes over the past decades. Now, we are witnessing a transition from simulations of simpler membrane models to multicomponent systems, culminating in realistic models of an increasing variety of cell types and organelles. Here, we review the state of the art in the field of realistic membrane simulations and discuss the current limitations and challenges ahead.

427 citations