A Comparative Study of the Influence of Sugars Sucrose, Trehalose, and Maltose on the Hydration and Diffusion of DMPC Lipid Bilayer at Complete Hydration: Investigation of Structural and Spectroscopic Aspect of Lipid–Sugar Interaction

Roy, Arpita; Dutta, Rupam; Kundu, Niloy; Banik, Debasis; Sarkar, Nilmoni

doi:10.1021/acs.langmuir.6b01115

Cited by 72 publications

(80 citation statements)

References 71 publications

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“…Finally, I want to discuss why cells started fusing together in the first place. Desiccation and desiccating agents, such as polyethylene glycol (PEG), are known to promote fusion of membranes by weakening hydrophobic interactions (Roy et al 2016;Erkut et al 2012;Pedrazzoli et al 2011;Hoekstra et al 2001;MacDonald 1985). Thus, it is quite possible that cell fusion first occurred by accident when cells were exposed to desiccating conditions.…”

Section: Appendix Amentioning

confidence: 99%

The thermodynamics of protein aggregation reactions may underpin the enhanced metabolic efficiency associated with heterosis, some balancing selection, and the evolution of ploidy levels

Ginn

2017

Progress in Biophysics and Molecular Biology

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Identifying the physical basis of heterosis (or "hybrid vigor") has remained elusive despite over a hundred years of research on the subject. The three main theories of heterosis are dominance theory, overdominance theory, and epistasis theory. Kacser and Burns (1981) identified the molecular basis of dominance, which has greatly enhanced our understanding of its importance to heterosis. This paper aims to explain how overdominance, and some features of epistasis, can similarly emerge from the molecular dynamics of proteins. Possessing multiple alleles at a gene locus results in the synthesis of different allozymes at reduced concentrations. This in turn reduces the rate at which each allozyme forms soluble oligomers, which are toxic and must be degraded, because allozymes co-aggregate at low efficiencies. The model developed in this paper can explain how heterozygosity impacts the metabolic efficiency of an organism. It can also explain why the viabilities of some inbred lines seem to decline rapidly at high inbreeding coefficients (F > 0.5), which may provide a physical basis for truncation selection for heterozygosity. Finally, the model has implications for the ploidy level of organisms. It can explain why polyploids are frequently found in environments where severe physical stresses promote the formation of soluble oligomers. The model can also explain why complex organisms, which need to synthesize aggregation-prone proteins that contain intrinsically unstructured regions (IURs) and multiple domains because they facilitate complex protein interaction networks (PINs), tend to be diploid while haploidy tends to be restricted to relatively simple organisms.

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Section: Appendix Amentioning

confidence: 99%

The thermodynamics of protein aggregation reactions may underpin the enhanced metabolic efficiency associated with heterosis, some balancing selection, and the evolution of ploidy levels

Ginn

2017

Progress in Biophysics and Molecular Biology

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“…When a desiccated membrane is rehydrated, the transition from the gel phase back to the liquid crystal phase does not occur uniformly across the membrane; some regions remain packed in the gel phase while others spread out in the liquid crystal phase (Fig. 2 d and e) [ 48 – 50 ] . Because of this non-uniform phase transition the membrane cannot expand to accommodate increased water volume during rehydration, ultimately causing transient holes to form in the membrane.…”

Section: Main Textmentioning

confidence: 99%

The biology of tardigrade disordered proteins in extreme stress tolerance

Hesgrove

Boothby

2020

Cell Commun Signal

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Disordered proteins have long been known to help mediate tolerance to different abiotic stresses including freezing, osmotic stress, high temperatures, and desiccation in a diverse set of organisms. Recently, three novel families of intrinsically disordered proteins were identified in tardigrades, microscopic animals capable of surviving a battery of environmental extremes. These three families include the Cytoplasmic-, Secreted-, and Mitochondrial- Abundant Heat Soluble (CAHS, SAHS, and MAHS) proteins, which are collectively termed Tardigrade Disordered Proteins (TDPs). At the level of sequence conservation TDPs are unique to tardigrades, and beyond their high degree of disorder the CAHS, SAHS, and MAHS families do not resemble one another. All three families are either highly expressed constitutively, or significantly enriched in response to desiccation. In vivo, ex vivo, and in vitro experiments indicate functional roles for members of each TDP family in mitigating cellular perturbations induced by various abiotic stresses. What is currently lacking is a comprehensive and holistic understanding of the fundamental mechanisms by which TDPs function, and the properties of TDPs that allow them to function via those mechanisms. A quantitative and systematic approach is needed to identify precisely what cellular damage TDPs work to prevent, what sequence features are important for these functions, and how those sequence features contribute to the underlying mechanisms of protection. Such an approach will inform us not only about these fascinating proteins, but will also provide insights into how the sequence of a disordered protein can dictate its functional, structural, and dynamic properties. Graphical abstract

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“…In fact, NDSs protect membranes of enlarged lipid vesicles against permeabilization in both aqueous solutions and in mammalian cells. [12,13] Thus, NDSs are relatively nontoxic to cells, and should be more effective than chloroquine for inhibiting lysosomal activity in the context of nonviral cargo delivery. Inspired by these studies, we hypothesized that pretreatment of cells with an NDS would enhance electrotransfer by reducing pDNA degradation without compromising cell viability.…”

Section: Pretreatment Of Cells With Nds Improves Electrotransfer Effimentioning

confidence: 99%

Redirecting Vesicular Transport to Improve Nonviral Delivery of Molecular Cargo

et al. 2020

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or genome editing, such as modification, augmentation, or depletion. The requirement can be achieved through delivery of molecular cargo (DNA, RNA, or protein) into cells, including zinc finger nucleases (ZFNs), [2] transcription activatorlike effector nucleases (TALENs), [3] and CRISPR and associated nucleases such as Cas9. [4] Thus, improving cargo delivery is critical for development of powerful tools used in cell engineering. Molecular cargo can be delivered into cells using either viral or nonviral methods. [5] Compared to nonviral ones, viral methods are in general more efficient. However, they are immunogenic, expensive, and potentially unsafe for clinical use. [6] In addition, viral vehicles have limited delivery capacity. [7] Nonviral methods such as electrotransfer (or electroporation) are increasingly being used in cell engineering. [8] Nonviral delivery is more cost-effective, multiplexable, and applicable to a wide variety of cargo than viral delivery, but currently considered to be inefficient in clinical applications. The low efficiency is often caused by enzymatic degradation of cargo in lysosomes before reaching the target site. Strategies to avoid degradation include facilitating endosomal escape, blocking vesicular transport to lysosomes, and inactivating lysosomal enzymes. Here we propose a new strategy called Pretreatment for Redirection of Endocytic and Autophagic Traffic (pTREAT) that increases the half-life of molecular cargo in cells. The increase is achieved by priming cells with a family of sugar molecules that are disaccharides or oligosaccharides (such as sucrose, trehalose, and raffinose) and cannot be broken down or degraded in mammalian cells. Treatment of cells with the nondegradable sugars (NDSs) can enlarge lysosomes and induce the formation of large nonacidic vesicles called amphisome-like bodies (ALBs), which hinder vesicular trafficking to lysosomes and redirect transport to ALBs. Both changes are reversible and lead to reduction in cargo degradation. To demonstrate the capabilities of the pTREAT method, we applied it to improving the efficiency of electrotransfer of several types of cargo-plasmid DNA, mRNA, Sleeping Beauty transposon, and the CRISPR/Cas9 system-into various cell types including human primary T cells, without compromising cell viability. Cell engineering relies heavily on viral vectors for the delivery of molecular cargo into cells due to their superior efficiency compared to nonviral ones. However, viruses are immunogenic and expensive to manufacture, and have limited delivery capacity. Nonviral delivery approaches avoid these limitations but are currently inefficient for clinical applications. This work demonstrates that the efficiency of nonviral delivery of plasmid DNA, mRNA, Sleeping Beauty transposon, and ribonucleoprotein can be significantly enhanced through pretreatment of cells with the nondegradable sugars (NDS), such as sucrose, trehalose, and raffinose. The enhancement is mediated by the incorporation of the NDS into cell membranes, causing enlar...

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A Comparative Study of the Influence of Sugars Sucrose, Trehalose, and Maltose on the Hydration and Diffusion of DMPC Lipid Bilayer at Complete Hydration: Investigation of Structural and Spectroscopic Aspect of Lipid–Sugar Interaction

Cited by 72 publications

References 71 publications

The thermodynamics of protein aggregation reactions may underpin the enhanced metabolic efficiency associated with heterosis, some balancing selection, and the evolution of ploidy levels

The thermodynamics of protein aggregation reactions may underpin the enhanced metabolic efficiency associated with heterosis, some balancing selection, and the evolution of ploidy levels

The biology of tardigrade disordered proteins in extreme stress tolerance

Redirecting Vesicular Transport to Improve Nonviral Delivery of Molecular Cargo

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