Budding transitions of fluid-bilayer vesicles: the effect of area-difference elasticity

Budding and vesiculation are prominent shape transformations of fluid lipid-bilayer vesicles. We discuss these transitions within the context of a curvature model which contains two types of bending energy. In addition to the usual local curvature elasticity κ, we include the effect of a relative areal stretching of the two monolayers. This area-difference elasticity leads to an effective nonlocal curvature energy characterized by another parameter κ¯. We argue that the two contributions to the curvature energy are typically comparable in magnitude. The model interpolates smoothly between the spontaneous-curvature model (κ¯=0) and the bilayer-couple model (κ¯→∞), discussed previously in the literature. Conceptually, this model is not new; however, neither its consequences nor its relation to experiment has previously been explored in detail. In particular, budding is discontinuous (first order) for small κ¯ but changes via a tricritical point to continuous (second order) for large κ¯. The order of the budding transition depends on both the ratio κ¯/κ (which is a material parameter) and the initial area difference between the inner and outer monolayers (which can be modified by appropriate treatment of the vesicle). Estimates suggest that, under typical laboratory conditions, the budding process should be discontinuous, in apparent disagreement with some recent experiments. Possible reasons for this discrepancy are discussed. We propose, in particular, that hysteretic effects are important and that the observed behavior may reflect a spinodal instability

Periodic Lamellipodial Contractions Correlate with Rearward Actin Waves

AbstractCellular lamellipodia bind to the matrix and probe its rigidity through forces generated by rearward F-actin transport. Cells respond to matrix rigidity by moving toward more rigid matrices using an unknown mechanism. In spreading and migrating cells we find local periodic contractions of lamellipodia that depend on matrix rigidity, fibronectin binding and myosin light chain kinase (MLCK). These contractions leave periodic rows of matrix bound β3-integrin and paxillin while generating waves of rearward moving actin bound α-actinin and MLCK. The period between contractions corresponds to the time for F-actin to move across the lamellipodia. Shortening lamellipodial width by activating cofilin decreased this period proportionally. Increasing lamellipodial width by Rac signaling activation increased this period. We propose that an actin bound, contraction-activated signaling complex is transported locally from the tip to the base of the lamellipodium, activating the next contraction/extension cycle

Dynamic Phase Transitions in Cell Spreading

We monitored isotropic spreading of mouse embryonic fibroblasts on fibronectin-coated substrates. Cell adhesion area versus time was measured via total internal reflection fluorescence microscopy. Spreading proceeds in well-defined phases. We found a power-law area growth with distinct exponents a_i in three sequential phases, which we denote basal (a_1=0.4+-0.2), continous (a_2=1.6+-0.9) and contractile (a_3=0.3+-0.2) spreading. High resolution differential interference contrast microscopy was used to characterize local membrane dynamics at the spreading front. Fourier power spectra of membrane velocity reveal the sudden development of periodic membrane retractions at the transition from continous to contractile spreading. We propose that the classification of cell spreading into phases with distinct functional characteristics and protein activity patterns serves as a paradigm for a general program of a phase classification of cellular phenotype. Biological variability is drastically reduced when only the corresponding phases are used for comparison across species/different cell lines.Comment: 4 pages, 5 figure

On the Nature of Information: How FAIR Digital Objects are Building-up Semantic Space

In this paper, we are concerned about the nature of information and how to gather and compose data with the help of so called FAIR digital objects (FDOs) in order to transform them to knowledge. FDOs are digital surrogates of real objects. The nature of information is intrinsically linked to the kind of questions one is asking. One might not ask a question or get philosophical about it. Answers depend on the data different disciplines gather about their objects of study. In Statistical Physics, classical Shannon entropy measures system order which in equilibrium just equals the heat exchanged with the environment. In cell biology, each protein carries certain functions which create specific information. Cognitive science describes how organisms perceive their environment via functional sensors and control behavior accordingly. Note that one can have function and control without meaning. In contrast, psychology is concerned with the assessment of our perceptions by assigning meaning and ensuing actions. Finally, philosophy builds logical constructs and formulates principles, in effect transforming facts into complex knowledge. All these statements make sense, but there is an even more concise way. Indeed, Luciano Floridi provides a precise and thorough classification of information in his central oeuvre On the Philosophy of Information (Floridi 2013). Especially, he performs a sequential construction to develop the attributes which data need to have in order to count as knowledge. Semantic information is necessarily well-formed, meaningful and truthful. Well-formed data becomes meaningful by action based-semantics of an autonomous-agent solving the symbol grounding problem (Taddeo and Floridi 2005) interacting with the environment. Knowledge is created then by being informed through relevant data accounted for. We notice that the notion of agency is crucial for defining meaning. The apparent gap between Sciences and Humanities (Bawden and Robinson 2020) is created by the very existence of meaning. Further, meaning depends on interactions & connotations which are commensurate with the effective complexity of the environment of a particular agent resulting in an array of possible definitions.In his classical paper More is different (Anderson 1972) discussed verbatim the hierarchical nature of science. Each level is made of and obeys the laws of its constituents from one level below with the higher-level exhibiting emergent properties like wetness of water assignable only to the whole system. As we rise through the hierarchies, there is a branch of science for each level of complexity; on each complexity level there are objects for which it is appropriate and fitting to build up vocabulary for the respective levels of description leading to formation of disciplinary languages. It is the central idea of causal emergence that on each level there is an optimal degree of coarse graining to define those objects in such a way that causality becomes maximal between them. This means there is emergence of informative higher scales in complex materials extending to biological systems and into the brain with its neural networks representing our thoughts in a hierarchy of neural correlates. A computational toolkit for optimal level prediction and control has been developed (Hoel and Levin 2020) which was conceptually extended to integrated information theory of consciousness (Albantakis et al. 2019). The large gap between sciences and humanities discussed above exhibits itself in a series of small gaps connected to the emergence of informative higher scales. It has been suggested that the origin of life may be identified as a transition in causal structure and information flow (Walker 2014). Integrated information measures globally how much the causal mechanisms of a system reduce the uncertainty about the possible causes for a given state. A measure of “information flow” that accurately captures causal effects has been proposed (Ay and Polani 2008). The state of the art is presented in (Ay et al. 2022) where the link between information and complexity is discussed. Ay et al single out hierarchical systems and interlevel causation. Even further, (Rosas et al. 2020) reconcile conflicting views of emergence via an exact information-theoretic approach to identify causal emergence in multivariate data. As information becomes differentially richer one eventually needs complexity measures beyond {Rn}. One may define generalized metrices on these spaces (Pirr&oacute 2009) measuring information complexity on ever higher hierarchical levels of information. As one rises through hierarchies, information on higher scale is usually gained by coarse graining to arrive at an effective, nevertheless exact description, on the higher scale. It is repeated coarse graining of syntactically well-ordered information layers which eventually leads to semantic information in a process which I conjecture to be reminiscent of renormalization group flow leading to a universal classification scheme. Thus, we identify scientific disciplines and their corresponding data sets as dual universality classes of physical and epistemic structure formation, respectively. Above the semantic gap, we may call this process quantification of the qualitative by semantic metrics. Indeed, (Kolchinsky and Wolpert 2018) explored for the first time quantitative semantic concepts in Physics in their 2018 seminal paper entitled Semantic information, autonomous agency and non-equilibrium statistical physics. Their measures are numeric variants of entropy. Semantic information is identified with ‘the information that a physical system has about its environment that is causally necessary for the system to maintain its own existence over time’.FDOs are employed in these processes in two fundamental ways. For practical implementations of FDO technology, see accompanying abstract (Wittenburg et al. 2022). First, the FAIR principles (Wilkinson et al. 2016) ensure that unconnected pieces of data may be percolated into an integrated data space. Percolation creates the information density needed to feed AI-driven built up of semantic space. Without FDOs we wouldn't have the gravity for this to occur. Second, the very structure of FDOs, capable of symmetry preserving or breaking fusion events into composed entities, makes them homologous to mathematical categories. This will proof to be a powerful tool to unravel the nature of information via analyzing its topological structure algebraically, especially when considering our conjecture concerning universality, classes of information and their possible instantiations on vastly different length and time scales, in effect explaining analogous structure formation

A lumped parameter model of endoplasm flow in Physarum polycephalum explains migration and polarization-induced asymmetry during the onset of locomotion.

The plasmodial slime mold Physarum polycephalum exhibits strong, periodic flow of cytoplasm through the veins of its network. In the special case of mesoplasmodia, a newly described starvation-induced, shape-constant morphotype, this periodic endoplasm streaming is the basis of locomotion. Furthermore, we presume that cytoplasm flow is also involved in signal transmission and signal processing. Mesoplasmodia motility resembles amoeboid locomotion. In contrast to other amoebae, however, mesoplasmodia move without extending pseudopods and retain a coherent, fan-shaped morphology throughout their steady locomotion. Attaining sizes of up to 2 mm2, mesoplasmodia are also much bigger than other amoebae. We characterize this particular type of locomotion and identify patterns of movement. By using the analogy between pulsatile fluid flow through a network of elastic tubes and electrical circuits, we build a lumped model that explains observed fluid flow patterns. Essentially, the mesoplasmodium acts as a low-pass filter, permitting only low-frequency oscillations to propagate from back to front. This frequency selection serves to optimize flow and reduces power dissipation. Furthermore, we introduce a distributed element into the lumped model to explain cell polarization during the onset of chemotaxis: Biochemical cues (internal or external) lead to a local softening of the actin cortex, which in turn causes an increased flow of cytoplasm into that area and, thus, a net forward movement. We conclude that the internal actin-enclosed vein network gives the slime mold a high measure of control over fluid transport, especially by softening or hardening, which in turn leads to polarization and net movement

Diacylglycerol-Rich Domain Formation in Giant Stearoyl-Oleoyl Phosphatidylcholine Vesicles Driven by Phospholipase C Activity

We have studied the effect of phospholipase C from Bacillus cereus and Clostridium perfringens (α-toxin) on giant stearoyl-oleoyl phosphatidylcholine (SOPC) vesicles. Enzyme activity leads to a binary mixture of SOPC and the diacylglycerol SOG, which phase separates into a SOPC-rich bilayer phase and a SOG-rich isotropic bulk-like domain embedded within the membrane, as seen directly by phase contrast microscopy. After prolonged enzymatic attack, all bilayer membranes are transformed into an isotropic pure SOG phase as characterized by fluorescence microscopy, differential scanning calorimetry, fluorescence anisotropy measurements, and small angle x-ray scattering. These domains may have biological relevance, serving as storage compartments for hydrophobic molecules and/or catalyzing cellular signaling events at their boundaries. Furthermore, in the early stages of asymmetric enzymatic attack to the external monolayer of giant vesicles, we observe a transient coupling of the second-messenger diacylglycerol to membrane spontaneous curvature, which decreases due to enzyme activity, before domain formation and final vesicle collapse occurs

FDO Project for Germany

In Germany there is much agreement on a necessary step towards convergence in the domain of digital entities across sectors given the increasing number of emerging data spaces in research, industry and public services. Therefore a group of FAIR Digital Objects (FDO) experts is working on a proposal that willdemonstrate the functionality of FDOs, their added value and the scalability of their components,establish an active FDO community across sectors and disciplines collaborating beyond the project,establish a network of key persons promoting and advancing the FDO standard and its applications in collaboration with the FDO Forum,implement a set of FDO applications for selected use cases from economy and applied research,advancing the further development of FDO specifications and their transformation to international standards andsupport the international FDO Forum initiative.In addition to the standard activities such as PR, outreach, organising meetings, management etc. the project is designed to support a few major pillars:A basic infrastructure for FDOs will be made professional and usable by everyone interested based on what has already been developed in the realm of the FDO Forum.Three use cases will be implemented to serve as demonstrators of FDOs: (a) A testbed of a set of repositories from research and industry including those that are applying standards developed in industrial initiatives such as Industry 4.0 and Int. Data Space Association. (b) Processes in time will be modelled with FDOs to demonstrate the secure mechanisms provided by FDOs. (c) Time will be spent on implementing methods where FDOs help to organise the huge data space as it will emerge in future. These use cases need to be worked out in the 3-year project that will act as demonstrators across borders.Three research motivated use cases will be tackled as well. The collaboratiing experts believe that it is important already now to introduce quantum computing and their possible impact on data spaces. The group iof experts also wants to not only implement FDO applications but also wants to investigate the foundations of FDOs. In addition, two concrete cases have been selected to demonstrate the value of FDOs (cancer database, tomography imaging).A Thinktank is planned to discuss many upcoming aspects related to FDOs and these large data spaces such as legal and ethical aspects, philosophy of information, social impact of digital transformation, codification of roles and usage scenarios, etc.Other goals of the project are to further develop the FDO specifications in close collaboration with the FDO Forum based on the insights from the implementations, transform the specifications to international standards, and set up certification mechanisms. These activities will be led by standardisation organisations (DIN, DKE) which are embedded in ISO/IEC groups.It is an explicit wish of the funding institution for FDOs to help to create a global integrated data space which requires a close collaboration with existing industrial initiatives such as Big Data Value Association, Industry 4.0, Int. Data Space Association, Gaia-X etc. Therefore, the project partners are currently in discussion with these initiatives to bring in their expertise and components wherever that makes sense. Industry for example is busy formalising “roles” and “usages” which is not a topic of the FDO Forum.The project partners are in close contact with the German FDO experts already contributing to the FDO Forum discussions to integrate their expertise where possible into the project. Although the project will focus on activities in Germany we will seek to reach out to other European countries and beyond. It is obvious that the project will need to invest in training from the beginning leveraging on the already existing knowledge in the FDO Forum, DONA and ePIC for example.We are currently in discussion with the funding agency in shaping this project with the intention to start it already in 2022. With this project being granted we hope to be able to advance the international attempts to achieve a higher degree of convergence and thus efficiency in the domain of digital objects

Dynamics of actin waves on patterned substrates : a quantitative analysis of circular dorsal ruffles

Circular Dorsal Ruffles (CDRs) have been known for decades, but the mechanism that organizes these actin waves remains unclear. In this article we systematically analyze the dynamics of CDRs on fibroblasts with respect to characteristics of current models of actin waves. We studied CDRs on heterogeneously shaped cells and on cells that we forced into disk-like morphology. We show that CDRs exhibit phenomena such as periodic cycles of formation, spiral patterns, and mutual wave annihilations that are in accord with an active medium description of CDRs. On cells of controlled morphologies, CDRs exhibit extremely regular patterns of repeated wave formation and propagation, whereas on random-shaped cells the dynamics seem to be dominated by the limited availability of a reactive species. We show that theoretical models of reaction-diffusion type incorporating conserved species capture partially the behavior we observe in our data.Published versio