The outer membrane (OM) is an essential barrier that guards Gram‐negative bacteria from diverse environmental insults. Besides functioning as a chemical gatekeeper, the OM also contributes towards the strength and stiffness of cells and allows them to sustain mechanical stress. Largely influenced by studies of Escherichia coli, the OM is viewed as a rigid barrier where OM proteins and lipopolysaccharides display restricted mobility. Here the discussion is extended to other bacterial species, with a focus on Myxococcus xanthus. In contrast (...) to the rigid OM paradigm, myxobacteria possess a relatively fluid OM. It is concluded that the fluidity of the OM varies across environmental species, which is likely linked to their evolution and adaptation to specific ecological niches. Importantly, a fluid OM can endow bacteria with distinct functions for cell‐cell and cell‐environment interactions. (shrink)

One persistent puzzle in the life sciences is the asymmetric lipid composition of the cellular plasma membrane: while the exoplasmic leaflet is enriched in lipids carrying predominantly saturated fatty acids, the cytoplasmic leaflet hosts preferentially lipids with (poly‐)unsaturated fatty acids. Given the high energy requirements necessary for cells to maintain this asymmetry, the question naturally arises regarding its inherent benefits. In this paper, we propose asymmetry to represent a potential solution for harmonizing two conflicting requirements for the plasma (...) class='Hi'>membrane: first, the need to build a barrier for the uncontrolled influx or efflux of substances; and second, the need to form a fluid and dynamic two‐dimensional substrate for signaling processes. We hence view here the plasma membrane as a composite material, where the exoplasmic leaflet is mainly responsible for the functional integrity of the barrier and the cytoplasmic leaflet for fluidity. We reinforce the validity of the proposed mechanism by presenting quantitative data from the literature, along with multiple examples that bolster our model. (shrink)

The biological membranes of eukaryotic cells harbor sensitive surveillance systems to establish, sense, and maintain characteristic physicochemical properties that ultimately define organelle identity. They are fundamentally important for membrane homeostasis and play active roles in cellular signaling, protein sorting, and the formation of vesicular carriers. Here, we compare the molecular mechanisms of Mga2 and Ire1, two sensors involved in the regulation of fatty acid desaturation and the response to unfolded proteins and lipid bilayer stress in order to identify their (...) commonalities and specializations. We will speculate on the cellular significance of membrane property sensors in other organelles and discuss their putative mechanisms. Based on these findings, we propose membrane property sensors as an emerging class of proteins with wide implications for organelle communication and function. (shrink)

You are what you eat – this well‐known phrase properly describes the phenomenon of the effects of diet on acute and chronic inflammation. Several lipids and lipophilic compounds that are delivered with food or are produced in situ in pathological conditions exert immunomodulatory activity due to their interactions with the plasma membrane. This group of compounds includes cholesterol and its oxidized derivatives, fatty acids, α‐tocopherol, and polyphenols. Despite their structural heterogeneity, all these compounds ultimately induce changes in plasma (...) class='Hi'>membrane architecture and fluidity. By doing this, they modulate the dynamics of plasma membrane receptors, such as TLR4. This receptor is activated by lipopolysaccharide, triggering acute inflammation during bacterial infection, which often leads to sepsis and is linked with diverse chronic inflammatory diseases. In this review, we discuss how the impact on plasma membrane properties contributes to the immunomodulatory activity of dietary compounds, pointing to the therapeutic potential of some of them.Also watch the Video Abstract. (shrink)

The combination of evolutionary with engineering principles will enhance synthetic biology. Conversely, synthetic biology has the potential to enrich evolutionary biology by explaining why some adaptive space is empty, on Earth or elsewhere. Synthetic biology, the design and construction of artificial biological systems, substitutes bio‐engineering for evolution, which is seen as an obstacle. But because evolution has produced the complexity and diversity of life, it provides a proven toolkit of genetic materials and principles available to synthetic biology. Evolution operates on (...) the population level, with the populations composed of unique individuals that are historical entities. The source of genetic novelty includes mutation, gene regulation, sex, symbiosis, and interspecies gene transfer. At a phenotypic level, variation derives from regulatory control, replication and diversification of components, compartmentalization, sexual selection and speciation, among others. Variation is limited by physical constraints such as diffusion, and chemical constraints such as reaction rates and membrane fluidity. While some of these tools of evolution are currently in use in synthetic biology, all ought to be examined for utility. A hybrid approach of synthetic biology coupled with fine‐tuning through evolution is suggested. (shrink)

This article argues for a shift in evolutionary metaphor-from fitness and the elimination of the less fit to fragility and passage through fragile periods of change. Childhood, for example, can be viewed as state of protected weakness, allowing time for more neural development, learning, and play. Similarly, evolutionary change can be released precisely when competitive pressure is relaxed. The fragility of evolution in time extends to several biological domains. The genetic system exhibits a surprising fluidity, whether from mobile genetic (...) elements or hypermutation due to stress. Through gene duplication, organisms build up redundancy, which can more readily diverge into novelty. With endo-symbiosis one organism becomes incorporated into another, merging genomes, membranes, and metabolisms. As a result novel structures and genetic restructuring occur, making for profound evolutionary change. In a sexual life cycle, gametes within a species group fuse and amplify subtle variation. Hybridization, or unions between atypical sexual partners, can cause instant speciation and an instability that leads to more evolution. With development organisms go through rapid morphological change and sensitive transition phases. Importantly, dissociation of developmental modules in both temporal and spatial ways allow for evolutionary novelty to emerge. Several lines of evidence lead to the hypothesis that the organism's inner matrix can respond to stresses and help shape a fluid genome. In a second article, three more biological domains will be examined, in which organisms and environment more obviously interpenetrate: the remarkably plastic neural/behavioral system, novel synergisms between organisms, and the multiple, complex dynamics of ecosystems-all of which help to generate life's outstanding diversity. Last, the protection of fragile human populations will be discussed. (shrink)

There is a question that has not been raised in the literature on Japan's regionalism: Why does it have a strong tendency toward making the boundary of the proposed East Asian community fluid? By looking back beyond the Greater East Asia Co-Prosperity Sphere of the 1940s, a method hitherto untried, the paper shows that this Japanese propensity was also present in the first half of the twentieth century, especially in the 1920s and 1930s. Moreover, both then and now, Japan did (...) not and does not have a firm adherence to an ideology. These are two similarities between the pre-World War II period and the present (from the 1960s). On the other hand, Japan's present international situation is very different from its pre-World War II position. The paper uses the logic of the comparative method, which states that in two cases that are different in most aspects but the same in some, one or some of the similarities may explain the other similarity or similarities. It concludes that in both periods, the lack of a firm commitment to an ideology explains Japan's prejudice toward boundary fluidity. This explanation has the potential to contribute to a more comprehensive, if not yet a general theory of Japan's approach to regionalism because it applies not only to the present, but to the past as well. And it has to be stressed, the past refers not only to the Greater East Asia Co-Prosperity Sphere of the 1940s but also to the decades before. (shrink)

This article seeks to enrich the social-theoretical and sociological approach to climate change by arguing in favour of a weak naturalistic ontology beyond the usually presupposed methodological sociologism or culturalism. Accordingly, attention is drawn to the elementary social forms that mediate between nature and the sociocultural form of life and thus figure as the central object of a critical sociological explanation of impediments retarding or preventing a transition to a sustainable global society. The argument is illustrated by a comparison of (...) the current situation of climate change to a similar situation some 10,000 years ago which conditioned the transition from hunting-gathering to farming. The crucial factor in the prehistoric transition had been the newly acquired cognitive fluidity, which not only became the defining feature of the modern human mind, but is also foundational of the corresponding social form of life. The cognitively fluid mind made possible new generative practices and the imagination of counterfactuals possessing an incursive force that is capable of transforming existing practices and social structures. The ultimate question, then, is twofold: whether there is enough potential left in the cognitively fluid mind for its societal significance to be activated to the benefit of a transformation of the current recalcitrant social formation; and whether we today are able and willing to recognize such potential and corresponding realizable possibilities upon which to act. (shrink)

What can the philosophy of agency learn from Nguyen’s book on games? The most important lesson concerns, to use Nguyen’s terms, the ‘layered’ structure of our agency and the ‘fluidity’ requ...

Lipid droplets (LDs) are ubiquitous, neutral lipid storage organelles that act as hubs of metabolic processes. LDs are structurally unique with a hydrophobic core that mainly consists of neutral lipids, sterol esters, and triglycerides, enclosed within a phospholipid monolayer. Nascent LD formation begins with the accumulation of neutral lipids in the endoplasmic reticulum (ER) bilayer. The ER membrane proteins such as seipin, LDAF1, FIT, and MCTPs are reported to play an important role in the formation of nascent LDs. As (...) the LDs grow, they unmix from the highly charged ER membrane to form mature LDs. LD biogenesis is an exciting, emerging research area, and herein, we discuss the recent progress in our understanding of the formation of eukaryotic nascent LDs. We focus on the role of ER membrane shaping proteins such as reticulons and reticulon‐like proteins, membrane lipids, and cytoskeleton proteins such as septin in the formation of nascent LDs. (shrink)

Most metazoan organisms have evolved a mildly acidified and calcium diminished sorting hub in the early secretory pathway commonly referred to as the Endoplasmic Reticulum‐Golgi intermediate compartment (ERGIC). These membranous vesicular‐tubular clusters are found tightly juxtaposed to ER subdomains that are competent for the production of COPII‐coated transport carriers. In contrast to many unicellular systems, metazoan COPII carriers largely transit just a few hundred nanometers to the ERGIC, prior to COPI‐dependent transport on to the cis‐Golgi. The mechanisms underlying formation and (...) maintenance of ERGIC membranes are poorly defined. However, recent evidence suggests an important role for Trk‐fused gene (TFG) in regulating the integrity of the ER/ERGIC interface. Moreover, in the absence of cytoskeletal elements to scaffold tracks on which COPII carriers might move, TFG appears to promote anterograde cargo transport by locally tethering COPII carriers adjacent to ERGIC membranes. This action, regulated in part by the intrinsically disordered domain of TFG, provides sufficient time for COPII coat disassembly prior to heterotypic membrane fusion and cargo delivery to the ERGIC. -/- . (shrink)

How do artists share, translate, reveal their imagination by using different semiotic systems; how can the audience partake in this imagination receiving only images, words, notation, sounds? Starting from artwork of the novelist Italo Calvino and the composers Helmut Lachenmann and Gyorgy Kurtag, this article addresses the relation among imagination, perception, remembrance and expression. The ‘images’ used, be they visual, verbal, auditory or haptic, are much more than images. They concentrate in themselves layers of subjective and intersubjective perceptual, cognitive and (...) emotive experiences. I will argue that imagination relies upon sensory fluidity. This allows us (1) to integrate sensorial experiences from different perceptual origins — synaesthesia, (2) to link past, present and future by way of sensorial and embodied patterns of remembrance — embodied sedimentation, and (3) to share intersubjective patterns of affect and effect, bridging idiosyncratic and universal human experiences. (shrink)

Both RalA and RalB interact with the ubiquitous calcium sensor, calmodulin (CaM). New structural and biophysical characterisation of these interactions strongly suggests that, in the native membrane‐associated state, only RalA can be extracted from the membrane by CaM and this non‐canonical interaction could underpin the divergent signalling roles of these closely related GTPases. The isoform specificity for RalA exhibited by CaM is hypothesised to contribute to the disparate signalling roles of RalA and RalB in mitochondrial dynamics. This would (...) lead to CaM shuttling RalA to the mitochondrial membrane but leaving RalB localisation unperturbed, and in doing so triggering mitochondrial fission pathways rather than mitophagy. (shrink)

It has long been known that the red blood cell contains a membrane skeleton that stabilizes the plasma membrane, determines its shape, and regulates the lateral distribution of the membrane glyco‐proteins to which it is attached. The way in which these functions are regulated in other cells has not been understood. It has now been shown that platelets also contain a membrane skeleton. In contrast to the membrane skeleton of the red blood cell, the platelet (...) membrane skeleton has actin‐binding protein, not spectrin, as a major component. The platelet membrane skeleton regulates the same cellular functions as the red blood cell membrane skeleton. Other cells may contain a membrane skeleton that is critical to their viability and normal functioning. (shrink)

Integral membrane proteins are found in all cellular membranes and fulfil many of the functions that are central to life. A critical step in the biosynthesis of membrane proteins is their insertion into the lipid bilayer. The mechanisms of membrane protein insertion and folding are becoming increasingly better understood, and efficient methods for the ab initio prediction of three‐dimensional protein structure from the primary amino acid sequence may be within reach. Already, the basic tools needed for engineering (...) and de novo design of integral membrane proteins seem to be at hand. (shrink)

Undoubtedly the Penrose-Hameroff Orch OR model may be considered as a good theory for describing information processing mechanisms and holistic phenomena in the human brain, but it doesn’t give us satisfactory explanation of human perception. In this work a new approach explaining our perception is introduced, which is in good agreement with Orch OR model and other mainstream science theories such as string theory, loop quantum gravity and holographic principle. It is shown that human perception cannot be explained in the (...) terms of elementary particles and we should introduce new indivisible holistic objects with geometry based on smooth infinitesimal analysis - elastic membranes. The example of such a membrane is our Universe which is an indivisible whole. It is shown that our perception may be considered as the result of elastic oscillations of two dimensional (2D) elastic membranes with closed topology embedded in our bodies. Only one elastic membrane responsible for its perceptions will correspond to the selected organism, but there may be other membranes, even at the cell level. In other words, reality may be considered as the process of time evolution of holistic energetically very weak macro objects - elastic membranes with the geometry based on smooth infinitesimal analysis. An embedded membrane in this multidimensional world will look different for the external and internal observers: from the outside it will look like a material object with smooth infinitesimal geometry, while from the inside our Universe-like space-time fabric. When interacting with elementary particles and other membranes, a membrane will transform their energy into its elastic energy (a new form of energy) - the energy of stretching of the infinitesimal segments. The theory postulates that these elastic deformations will not be observable from the point of view of the internal observer. Heisenberg’s uncertainty principle will work in this physics only from the point of view of the internal observer. For the external observer each embedded elastic membrane may be stretched and even a very small region will become observable. For example, living organisms play the role of internal observers of the Universe, and at the same time they serve as external observers for 2D membranes embedded into our Universe. We can observe our 2D self-membranes through our perceptions, which are encoded in elastic oscillations of the elastic membrane. According to the theory, elastic membranes occupy energetically favorable positions around microtubules involved into Orch OR. The theory not only gives us a really multidimensional holistic picture of reality, but it also provides us with a new method for understanding such phenomena as perception, self-awareness and will. (shrink)

Corporate social responsibility (CSR) is a relatively undeveloped concept despite its increasing importance to corporations. One difficulty is the possible inexactness of CSR. Another is the apparent reluctance by regulatory authorities and policy makers to intervene in the area. This is largely a result of inhibitions created by traditional approaches to company law with emphasis on shareholder protection and financial disclosure. The consequence is the stultification of independent development of CSR by tying social issues to financial performance. This attitude might (...) not be unconnected to the theoretical and practical challenges in justifying CSR and defining its scope. The underlying impediment is a factual and theoretical failure to distinguish ‘instrumental’ and ‘pure’ (ethical) CSR. This article demonstrates that ethical CSR highlights the role of regulation, and a principal stance is that regulation is neither incompatible nor irreconcilable with ethical CSR. The article argues that cognizance of the intrinsic moral justification of ‘pure’ CSR is required for delineating the scope of CSR as well as for clarifying the desirability and extent of its regulation. It argues that the dynamic history and visage of multinational corporate corruption illuminates the fluidity of the regulation–CSR relationship. The current and widening backlash against transnational corporate corruption is, arguably, a demonstration of the position that regulation and CSR are not mutually exclusive and absolute concepts. This article submits that recognition and application of this ‘ethical’ and ‘instrumental’ CSR distinction is fundamental to the development of CSR and resolution of connected questions of regulation. (shrink)

Microfilament interactions with the plasma membranes of animal cells appear to vary with cell type and localization. In the erythrocyte, actin oligomers are associated with the membrane via spectrin and ankyrin. The ends of stress fibers in cultured cells, such as fibroblasts, are attached to the plasma membrane at focal adhesion sites and may involve the protein vinculin as a linking protein. In intestinal brush border microvilli a 110,000 dalton protein links the microfilament bundles to sites on the (...) microvillus. A transmembrane complex containing actin stably associated with a cell surface glycoprotein can be isolated from ascites tumor cell microvilli and can be obtained still associated with microfilaments by gentle extraction and gradient centrifugation of the microvilli. These varied interaction mechanisms are believed to be needed to satisfy the different structural and dynamic requirements of the particular systems. (shrink)

The synthesis of biological membranes requires the insertion of proteins into a lipid bilayer. The rough endoplasmic reticulum of eukaryotic cells is a principal site of membrane biogenesis. The insertion of proteins into the membrane of the endoplasmic reticulum is mediated by a resident proteinaceous machinery. Over the last five years several different experimental approaches have provided information about the components of the machinery and how it may function.

Tubulin is the ubiquitous protein that makes up the walls of the cytoskeletal elements known as microtubules. These 20 nm diameter cylindrical fibers are the spindle fibers for mitosis, provide the skeletal framework for cellular elongation, constitute the major structural and motile elements of cilia and flagella and probably play a number of other roles in eukaryote cells. In the electron microscope, they are never seen to attach or protrude directly into or on cellular membranes. It was therefore with much (...) skepticism that cell biologists responded to recent claims purporting to show that tubulin is (or can be) a membrane protein. This skepticism comes from a bias based on the generally understood function of cytoskeletal proteins as representing the intracellular ‘bones’ of cells. The traditional thinking was that microtubules may attach to cellular membranes but only via a cross‐linking connecting protein. In recent years, however, an increasing number of workers have come to believe that tubulin can exist as a normal membrane protein possibly independent of its role in microtubule function. (shrink)

Two kinds of membrane contacts in the vertebrate lens are described. Fiber gap junctions are domains where small molecules can pass between lens cells. Membrane structures of ball‐and‐socket type interlock adjacent lens fibers and thus contribute to the structural integrity of the lens. Both of these membrane contacts appear crucial for the maintenance of lens transparency.

It is common to say that the origin of the membrane potential is attributed to transmembrane ion transport, but it is theoretically possible to explain its generation by the mechanism of ion adsorption. It has been previously suggested that the ion adsorption mechanism even leads to potential formulae identical to the famous Nernst equation or the Goldman-Hodgkin-Katz equation. Our further analysis, presented in this paper, indicates that the potential formula based on the ion adsorption mechanism leads to an equation (...) that is a function of the surface charge density of the material and the surface potential of the material. Furthermore, we have confirmed that the equation holds in all the different experimental systems that we have studied. This equation appears to be a key equation that governs the characteristics of the membrane potential in all systems. (shrink)

This paper considers two among the several points of intersection in the work of Roberto Esposito and Jacques Derrida. First, and most obviously: in the context of conceptualizing community, and more broadly, Esposito and Derrida have elaborated concepts of immunity and auto-immunity to refer to auto-destructive modes of defense which profoundly threaten what – seemingly – ought to have been safeguarded through their mechanism. The second point of proximity is the use both make of figures of maternity and birth in (...) these conceptualizations. This comparison not only illuminates the differing philosophical commitments of Derrida and Esposito but also offers a means of challenging the fate of sexual difference in the work of Esposito. (shrink)

Membranous organelles allow sub‐compartmentalization of biological processes. However, additional subcellular structures create dynamic reaction spaces without the need for membranes. Such membrane‐less organelles (MLOs) are physiologically relevant and impact development, gene expression regulation, and cellular stress responses. The phenomenon resulting in the formation of MLOs is called liquid–liquid phase separation (LLPS), and is primarily governed by the interactions of multi‐domain proteins or proteins harboring intrinsically disordered regions as well as RNA‐binding domains. Although the presence of RNAs affects the formation (...) and dissolution of MLOs, it remains unclear how the properties of RNAs exactly contribute to these effects. Here, the authors review this emerging field, and explore how particular RNA properties can affect LLPS and the behavior of MLOs. It is suggested that post‐transcriptional RNA modification systems could be contributors for dynamically modulating the assembly and dissolution of MLOs. (shrink)

I propose a neuroscience and animat research-inspired model and a thought experiment to test the hypothesis of a developmental relation between fluid and crystallized intelligence. I propose that crystallized intelligence is the result of well-defined activities and structures, whereas fluid intelligence is the physiological catalytic adaptation mechanism responsible for coordinating and regulating the crystallized structures. We can design experiments to reproduce exemplified normal and anomalous phenomena, especially disorders, and study possible cognitive treatments. (Published Online April 5 2006).

Inspiration from Bauman’s analyses of„ liquid modernity” can be drawn to trace the transformations that love and hatred, as methods of solving the fundamental contradictions of human existence – stemming from the opposition between nature and culture, body and soul, death and immortality – undergo in these conditions. Those contradictions are manifested and reproduced in the relations between the subject and the other, relations of dividing and uniting, seeking transcendence. Analyzing these relations allows one to uncover the essence of death, (...) love, and hate between individuals and between communities of all sizes, including nations. Recognizing the essence of love and a subject‐object relationship, in which the truth of its subject and of onself is sought, a mutual surrender that transcendents the difference between egoism and altruism, and building a feeling of unity and dignity in a confrontation with inescapability of death – allows for the protection of those values against the destructive blows of hate. (shrink)

The liver was used widely in early studies of polarised transport but has been largely overlooked in recent years, mostly because of the development of epithelial cell lines which provide more tractable experimental systems. The majority of membrane proteins and lipids reach the hepatocyte apical membrane by transcytosis and it remains unclear whether there is a direct route for apical targeting, although the pathways present have yet to be fully characterised. The recent development of systems that allow hepatocyte (...) transport processes to be studied in culture and the observation that transcytosis can be significantly stimulated under physiological conditions suggest that hepatocytes have a role to play in future studies of polarised transport. This review discusses the known features of polarised membrane traffic in hepatocytes and contrasts them with the characteristics of vesicular transport in other epithelial cell types. (shrink)

We examine one of the well-known mathematical works of Abraham bar Ḥiyya: Ḥibbur ha-Meshiḥah ve-ha-Tishboret, written between 1116 and 1145, which is one of the first extant mathematical manuscripts in Hebrew. In the secondary literature about this work, two main theses have been presented: the first is that one Urtext exists; the second is that two recensions were written—a shorter, more practical one, and a longer, more scientific one. Critically comparing the eight known copies of the Ḥibbur, we show that (...) contrary to these two theses, one should adopt a fluid model of textual transmission for the various manuscripts of the Ḥibbur, because neither of these two theses can account fully for the changes among the various manuscripts. We hence offer to concentrate on the typology of the variations among the various manuscripts, dealing with macro-changes (such as omissions or additions of proofs, additional appendices or a reorganization of the text itself), and micro-changes (such as textual and pictorial variants). (shrink)

The myelin basic proteins are a set of peripheral membrane polypeptides which play an essential role in myelination. Their most well‐documented property is the unique ability to ‘seal’ the cytoplasmic aspects of the myelin membrane, but this is probably not the only function for these highly charged molecules. Despite extensive homology, the individual myelin basic proteins (MBPs) exhibit different expression patterns and biochemical properties, and so it is now believed that the various isoforms are not functionally equivalent in (...) myelinating cells. We now think that while the major MBPs are intracellular adhesion molecules, some of the quantitatively less abundant isoforms that are expressed very early in development may have regulatory effects on the myelination program. (shrink)

The human immune system can directly lyse invading micro‐organisms and aberrant host cells by generating pores in the cell envelope, called membrane attack complexes (MACs). Recent studies using single‐particle cryoelectron microscopy have revealed that the MAC is an asymmetric, flexible pore and have provided a structural basis on how the MAC ruptures single lipid membranes. Despite these insights, it remains unclear how the MAC ruptures the composite cell envelope of Gram‐negative bacteria. Recent functional studies on Gram‐negative bacteria elucidate that (...) local assembly of MAC pores by surface‐bound C5 convertase enzymes is essential to stably insert these pores into the bacterial outer membrane (OM). These convertase‐generated MAC pores can subsequently efficiently damage the bacterial inner membrane (IM), which is essential for bacterial killing. This review summarizes these recent insights of MAC assembly and discusses how MAC pores kill Gram‐negative bacteria. Furthermore, this review elaborates on how MAC‐dependent OM damage could lead to IM destabilization, which is currently not well understood. A better understanding on how MAC pores kill bacteria could facilitate the future development of novel strategies to treat infections with Gram‐negative bacteria. (shrink)

One of the earliest structural changes observed in cells in response to many extracellular factors is membrane ruffling: the formation of motile cell surface protrusions containing a meshwork of newly polymerized actin filaments. It is becoming clear that actin reorganization is an integral part of early signal transduction pathways, and that many signalling molecules interact with the actin cytoskeleton. The small GTP‐binding protein Rac is a key regulator of membrane ruffling, and proteins that can regulate Rac activity, such (...) as Bcr, are likely to act on this signalling pathway. In addition, several previously characterized signal transducing molecules are implicated in the membrane‐ruffling response, including Ras, the adaptor protein Grb2, phosphatidyl inositol 3‐kinase, phospholipase A2 and phorbol ester‐responsive proteins. Changes in polyphosphoinositide metabolism and intracellular Ca2+ levels may also play a role. A number of actin‐binding and organizing proteins localize to membrane ruffles and are potential targets for these signal transducing molecules. (shrink)

In the context of 1960s research on biological membranes, scientists stumbled upon a curiously coloured material substance, which became called the “purple membrane.” Interactions with the material as well as chemical analyses led to the conclusion that the microbial membrane contained a photoactive molecule similar to rhodopsin, the light receptor of animals’ retinae. Until 1975, the find led to the formation of novel objects in science, and subsequently to the development of a field in the molecular life sciences (...) that comprised biophysics, bioenergetics as well as membrane and structural biology. Furthermore, the purple membrane and bacteriorhodopsin, as the photoactive membrane transport protein was baptized, inspired attempts at hybrid bio-optical engineering throughout the 1980s. A central motif of the research field was the identification of a functional biological structure, such as a membrane, with a reactive material substance that could be easily prepared and manipulated. Building on this premise, early purple membrane research will be taken as a case in point to understand the appearance and transformation of objects in science through work with material substances. Here, the role played by a perceptible material and its spontaneous change of colour, or reactivity, casts a different light on objects and experimental practices in the late twentieth century molecular life sciences. With respect to the impact of chemical working and thinking, the purple membrane and rhodopsins represent an influential domain straddling the life and chemical sciences as well as bio- and material technologies, which has received only little historical and philosophical attention. Re-drawing the boundary between the living and the non-enlivened, these researches explain and model organismic activity through the reactivity of macromolecular structures, and thus palpable material substances. (shrink)

Fission of cellular membranes is ubiquitous and essential for life. Complex protein machineries, such as the dynamin and ESCRT spirals, have evolved to mediate membrane fission during diverse cellular processes, for example, vesicle budding. A new study suggests that non-specialized membrane-bound proteins can induce membrane fission through mass action due to protein crowding. Because up to 2/3 of the mass of cellular membranes is contributed by proteins, membrane protein crowding is an important physiological parameter. Considering the (...) complexity of membrane shape transitions during a fission reaction, spatial and temporal variability in protein distribution, and the abundance of intrinsically disordered regions in proteins on an invaginating membrane, protein crowding can have diverse consequences for fission in the cell. The question is, how and to what extent this mechanism combines with the action of dedicated fission machineries. Membrane fission, which is required for formation of vesicles or cytokinesis, can be carried out by specialized proteins like dynamin and the ESCRT complex. Recent work suggests that fission of cellular membranes, which are densely packed with proteins, can also be induced by protein crowding due to high entropic tension. (shrink)

Extracorporeal membrane oxygenation (ECMO) is a form of life support for cardiac and/or pulmonary failure with unique ethical challenges compared to other forms of life support. Ethical challenges with ECMO exist when conventional standards of care apply, and are exacerbated during periods of absolute ECMO scarcity when “crisis standards of care” are instituted. When conventional standards of care apply, we propose that it is ethically permissible to withhold placing patients on ECMO for reasons of technical futility or when patients (...) have terminal, short-term prognoses that are untreatable by ECMO. Under crisis standards of care, it is ethically permissible to broaden exclusionary criteria to also withhold ECMO from patients who have a low likelihood of recovery, to maximize the overall number of lives saved. Unilateral withdrawal of ECMO against a patient’s preferences is unethical under conventional standards of care, but is ethical under crisis standards of care to increase access to ECMO to others in society. ECMO should only be rationed when true scarcity exists, and allocation protocols should be transparent to the public. When rationing must occur under crisis standards of care, it is imperative that oversight bodies assess for inequities in the allocation of ECMO and make frequent changes to improve any inequities. (shrink)

Cell membranes experience frequent stretching and poking: from cytoskeletal elements, from osmotic imbalances, from fusion and budding of vesicles, and from forces from the outside. Are the ensuing changes in membrane tension localized near the site of perturbation, or do these changes propagate rapidly through the membrane to distant parts of the cell, perhaps as a mechanical mechanism of long‐range signaling? Literature statements on the timescale for membrane tension to equilibrate across a cell vary by a factor (...) of ≈106. This study reviews and discusses how apparently contradictory findings on tension propagation in cells can be evaluated in the context of 2D hydrodynamics and poroelasticity. Localization of tension in the cell membrane is likely critical in governing how membrane forces gate ion channels, set the subcellular distribution of vesicle fusion, and regulate the dynamics of cytoskeletal growth. Furthermore, in this study, it is proposed that cells can actively regulate the degree to which membrane tension propagates by modulating the density and arrangement of immobile transmembrane proteins. Also see the video abstract here https://youtu.be/T6K7AIAqqBs. (shrink)

In this article, it is hypothesized that a fundamental chemical reactivity exists between some non‐lipid constituents of cellular membranes and ester‐based lipids, the significance of which is not generally recognized. Many peptides and smaller organic molecules have now been shown to undergo lipidation reactions in model membranes in circumstances where direct reaction with the lipid is the only viable route for acyl transfer. Crucially, drugs like propranolol are lipidated in vivo with product profiles that are comparable to those produced in (...) vitro. Some compounds have also been found to promote lipid hydrolysis. Drugs with high lytic activity in vivo tend to have higher toxicity in vitro. Deacylases and lipases are proposed as key enzymes that protect cells against the effects of intrinsic lipidation. The toxic effects of intrinsic lipidation are hypothesized to include a route by which nucleation can occur during the formation of amyloid fibrils. (shrink)