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bioRxiv2026

LATEER: Low-Cost Open-Source Platform for Electrical Stimulation and TEER Measurement in Human Cardiomyocytes

Electrical stimulation (ES) and transepithelial/transendothelial electrical resistance (TEER) measurements are essential techniques in cell biology and tissue engineering, yet commercial devices for these applications cost between USD 2,500-9,000 and typically offer only one functionality. We present LATEER (Low-cost Arduino-based TEER and Electrical stimulation device), an open-source hardware platform that combines both ES and TEER measurement capabilities at a total cost below USD 100. The device features four independent channels, configurable pulsatile signals (amplitude up to 8.2 V, frequency 0.1-500 Hz, pulse width [≥]0.1 ms), and a resistance measurement range of 300 {Omega} to 1 M{Omega}, with <5% error for R {gtrsim} 4.7 k{Omega}. LATEER uses commercially available graphite pencil leads as electrodes ([~]USD 2 vs. USD 350 for commercial Ag/AgCl electrodes), which demonstrated excellent biocompatibility in cell culture. The system includes 3D-printed electrode holders compatible with standard 12-well and 24-well plates, allowing microscope visualization without electrode removal, and a Python-based graphical user interface for parameter configuration and real-time data acquisition. Because the electrodes remain fixed in the plate lid and only a single cable enters the incubator, both stimulation and resistance measurement can run continuously under standard culture conditions (37 {degrees}C, 5% CO2) without removing the plate or repositioning the electrodes, avoiding the temperature excursions and placement variability inherent to manual chopstick measurements. Validation with human pluripotent stem cell-derived cardiomyocytes demonstrated reliable frequency capture (electrical pacing) of the contracting monolayer, with a capture threshold between 250 and 400 mV/mm and controlled pacing across the 0.5-5 Hz range. TEER functionality was verified with mesenchymal stem cells, where the device resolved cell-density-dependent differences in electrical resistance in real time. All design files, firmware, and software are freely available under the CERN-OHL-S v2 license, enabling replication and customization by research laboratories worldwide. HighlightsO_LIAn open-source device combines electrical stimulation and TEER measurement under $100 C_LIO_LIGraphite electrodes offer biocompatibility at 0.6% cost of commercial alternatives C_LIO_LIFour independent channels with configurable parameters and real-time data logging. C_LIO_LIContinuous run setup in-incubator; no electrode repositioning needed C_LIO_LIValidated with stem cell-derived cardiomyocytes, achieving frequency capture (threshold 250-400 mV/mm) C_LIO_LI3D-printed holders enable microscope visualization without electrode removal C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=78 SRC="FIGDIR/small/743263v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@19e2eeorg.highwire.dtl.DTLVardef@181aeb4org.highwire.dtl.DTLVardef@f4b77aorg.highwire.dtl.DTLVardef@39cced_HPS_FORMAT_FIGEXP M_FIG C_FIG Specifications Table O_TBL View this table: org.highwire.dtl.DTLVardef@bd04c1org.highwire.dtl.DTLVardef@1831c4eorg.highwire.dtl.DTLVardef@b7698forg.highwire.dtl.DTLVardef@1736519org.highwire.dtl.DTLVardef@f2595c_HPS_FORMAT_FIGEXP M_TBL C_TBL

bioengineering↗

bioRxiv2025

PRC2 Restricts Malignant Peripheral Nerve Sheath Tumorigenesis in a Genetically Engineered Mouse Model of MPNST

Polycomb Repressive Complex 2 (PRC2), which normally regulates transcriptional silencing, chromatin compaction, and stem cell biology, has both oncogenic and tumor suppressor roles in cancer development depending on tumor type. Malignant peripheral nerve sheath tumor (MPNST), characterized by NF1, CDKN2A and PRC2 loss, is an aggressive subtype of sarcoma with poor prognosis and no effective therapy. In high-grade human MPNSTs, inactivating mutations in PRC2 core components SUZ12 or EED are prevalent and contributes to oncogenic transformation and progression of MPNST. How PRC2 inactivation contributes to MPNST pathogenesis, however, remains incompletely understood. Here we show that genetic inactivation of Eed in addition to Nf1 and Cdkn2a in the Schwann-progenitor lineage leads to widespread tumorigenesis within the sciatic nerve compartment of mice. In contrast, loss of Nf1 and Cdkn2a is insufficient to drive tumorigenesis in the sciatic nerve but leads to MPNST development in other anatomic locations with a longer latency. Single-nucleus multiome sequencing of the sciatic nerves revealed that PRC2-loss reprograms Nf1/Cdkn2a-deficient Schwann-lineage cells toward a dedifferentiated, neural crest stem cell-like state that resembles the transcriptomic signatures of human PRC2-loss MPNST. Together, these findings suggest a context-dependent tumor suppressive role for PRC2 within the sciatic nerve and establish a novel mouse model that recapitulates human PRC2-loss MPNST. SIGNIFICANCEWe present a novel genetically engineered mouse model that faithfully recapitulates human PRC2-loss MPNST, enabling mechanistic and preclinical studies of malignant transformation in the context of PRC2 loss.

cancer biology↗

bioRxiv2024

Concatemer Assisted Stoichiometry Analysis (CASA): a targeted mass spectrometry method for protein quantification

Large multi-protein machines are central to multiple biological processes. However, stoichiometric determination of protein complex subunits in their native states presents a significant challenge. This study addresses the limitations of current tools in accuracy and precision by introducing concatemer-assisted stoichiometry analysis (CASA). CASA leverages stable isotope-labeled concatemers and liquid chromatography parallel reaction monitoring mass spectrometry (LC-PRM-MS) to achieve robust quantification of proteins with sub-femtomole sensitivity. As a proof-of-concept, CASA was applied to study budding yeast kinetochores. Stoichiometries were determined for ex vivo reconstituted kinetochore components, including the canonical H3 nucleosomes, centromeric (Cse4CENP-A) nucleosomes, centromere proximal factors (Cbf1 and CBF3 complex), inner kinetochore proteins (Mif2CENP-C, Ctf19CCAN complex), and outer kinetochore proteins (KMN network). Absolute quantification by CASA revealed Cse4CENP-A as a cell-cycle controlled limiting factor for kinetochore assembly. These findings demonstrate that CASA is applicable for stoichiometry analysis of multi-protein assemblies. SummaryThis study presents Concatemer-Assisted Stoichiometry Analysis (CASA) to address a common challenge in cell biological research: quantifying the number of each protein subunit in a native protein complex.

molecular biology↗

bioRxiv2025

Membrane Interfacial Potential Governs Surface Condensation andFibrillation of α-Synuclein in Neurons

Biomolecular condensates formed via liquid-liquid phase separation (LLPS) are essential for cellular organization. -Synuclein, an amyloidogenic protein linked to Parkinsons Disease (PD), undergoes phase separation at high concentrations, but the influence of lipid membranes on this process remains unclear. Here, combining in vitro reconstitution, cell biology, and simulations, we show that membranous interfaces promote -Synuclein condensation at physiologically relevant sub-critical concentrations ([~]10 nM) without crowding agents. Notably, condensation occurs only on membranes with a specific stoichiometry of lipids, underscoring the role of interfacial potential. These condensates serve as nucleation sites for fibril formation, leading to membrane deformation and rupture. A lattice gas model reveals this behavior as a prewetting-like transition, where an attractive membrane induces local phase separation below the bulk saturation concentration. Indeed altering interfacial potential by lipid composition and membrane depolarization not only drastically changes -Synuclein puncta size and number but also triggers their release from neurons. These findings reveal the crucial role of lipid membrane interfaces in regulating -Synuclein condensation, aggregation and release, shedding light on a potential mechanism of their cell-to-cell propagation during neurodegeneration.

biophysics↗

bioRxiv2019

An Integrated Multiscale, Multicellular Skin Model

Skin is our primary barrier to the outside world, protecting us from physical, biological and chemical threats. Developing innovative products that preserve and improve skin barrier function requires a thorough understanding of the mechanisms underlying barrier response to topical applications. In many fields, computer simulations already facilitate understanding, thus accelerating innovation. Simulations of software models allow scientists to test hypothesized mechanisms by comparing predicted results to physical observations. They also enable virtual product optimization, without physical experiments, once mechanisms have been validated. The physical accessibility and abundant knowledge of skin structure makes it a prime candidate for computational modeling. In this article, we describe a computational multiscale multicellular skin model used to simulate growth and response of the epidermal barrier. The model integrates several modeling styles and mathematical frameworks including ordinary differential equations, partial differential equations, discrete agent-based modeling and discrete element methods. Specifically, to capture cell biology and physical transport, we combined four distinct sub-models from existing literature. We also implemented methods for elastic biomechanics. Our software implementation of the model is compatible with the high-performance computing simulation platform Biocellion. The integrated model recapitulates barrier formation, homeostasis and response to environmental, chemical and mechanical perturbation. This work exemplifies methodology for integrating models of vastly different styles. The methodology enables us to effectively build on existing knowledge and produce "whole-system" tissue models capable of displaying emergent properties. It also illustrates the inherent technical difficulties associated with the mounting complexity of describing biological systems at high fidelity. Among the challenges are validation of the science, the mathematical representations approximating the science and the software implementing these representations. Responsibility for a discrepancy observed between in silico and in vitro results may as easily lie at one of these three levels as at another, demanding that any sustainable modeling endeavor engage expertise from biology, mathematics and computing.

systems biology↗

bioRxiv2020

Site-specific recombination between inverted target sites generates dicentric/acentric chromosomes.

Site-specific recombinases are widely used tools for analysis of genetics, development and cell biology, and many schemes have been devised to alter gene expression by recombinase-mediated DNA rearrangements. Because the FRT and lox target sites for the commonly used FLP and Cre recombinases are asymmetrical, and must pair in the same direction to recombine, construct design must take into account orientation of the target sites. Both direct and inverted configurations have been used. However, the consequence of recombination between target sites on sister chromatids is frequently overlooked. This is especially consequential with inverted target sites, where exchange between oppositely oriented target sites on sisters will produce dicentric and acentric chromosomes. By using constructs that have inverted target sites in Drosophila melanogaster and in mice, we show here that dicentric chromosomes are produced in the presence of recombinase, and that the frequency of this event is quite high. The negative effects on cell viability and behavior can be significant, and should be considered when using such constructs.

genetics↗

bioRxiv2020

Photobleaching step analysis for robust determination of protein complex stoichiometries

The composition of cellular structures on the nanoscale is a key determinant of macroscopic functions in cell biology and beyond. Different fluorescence single-molecule techniques have proven ideally suited for measuring protein copy numbers of cellular structures in intact biological samples. Of these, photobleaching step analysis poses minimal demands on the microscope and its counting range has significantly improved with more sophisticated algorithms for step detection, albeit at an increasing computational cost. Here, we present a comprehensive framework for photobleaching step analysis, optimizing both data acquisition and analysis. To make full use of the potential of photobleaching step analysis, we evaluate various labelling strategies with respect to their molecular brightness and photostability. The developed analysis algorithm focuses on automation and computational efficiency. Moreover, we benchmark the framework with experimental data acquired on DNA origami labeled with defined fluorophore numbers to demonstrate counting of up to 35 fluorophores. Finally, we show the power of the combination of optimized trace acquisition and automated data analysis for robust protein counting by counting labelled nucleoporin 107 in nuclear pore complexes of intact U2OS cells. The successful in situ application promotes this framework as a new resource enabling cell biologists to robustly determine the stoichiometries of molecular assemblies at the single-molecule level in an automated fashion.

biophysics↗

bioRxiv2020

Spectrin Interactome under normal and HbE-disease conditions

Spectrin, the major component of the erythrocyte membrane skeleton is a key player in red cell biology. It has a significant role in signalling pathways and as such knowledge of spectrin interactors becomes crucial. Here we report the cytosolic interactome of human erythroid spectrin (ProteomeXchange id: PXD021525). This is to the best of our knowledge the first report of the interactome of human erythroid spectrin. We have further investigated the spectrin interactome under HbE disease conditions. Our findings indicate that there is no difference in the identity of the proteins interacting with spectrin between normal and disease conditions. However relative abundance of the interacting partners is seen to change. Very interestingly the interacting chaperone proteins, heme-containing proteins and redox active proteins are seen to be up-regulated in HbE disease state. This is consistent with our previous observation that presence of oxidation prone hemoglobin variants leads to an increase of redox regulators and chaperones in the red cell proteome. Spectrin can also interact with horse radish peroxidase and oxidatively crosslink hemoglobin, which has possible implications in oxidative stress management. Since a large fraction of spectrin interacting proteins are chaperones and redox active proteins, it is possible that spectrin may have a broader role in redox regulation, especially in cases where there are unstable hemoglobin variants present.

biochemistry↗

bioRxiv2023

From autopoiesis to self-optimization: Toward an enactive model of biological regulation

The theory of autopoiesis has been influential in many areas of theoretical biology, especially in the fields of artificial life and origins of life. However, it has not managed to productively connect with mainstream biology, partly for theoretical reasons, but arguably mainly because deriving specific working hypotheses has been challenging. The theory has recently undergone significant conceptual development in the enactive approach to life and mind. Hidden complexity in the original conception of autopoiesis has been explicated in the service of other operationalizable concepts related to self-individuation: precariousness, adaptivity, and agency. Here we advance these developments by highlighting the interplay of these concepts with considerations from thermodynamics: reversibility, irreversibility, and path-dependence. We interpret this interplay in terms of the self-optimization model, and present modeling results that illustrate how these minimal conditions enable a system to re-organize itself such that it tends toward coordinated constraint satisfaction at the system level. Although the model is still very abstract, these results point in a direction where the enactive approach could productively connect with cell biology.

systems biology↗

bioRxiv2022

Paradigm shift in eukaryotic biocrystallization

Despite the widespread occurrence of crystalline inclusions in unicellular eukaryotes, scant attention has been paid to their composition, functions, and evolutionary origins, assuming just their inorganic contents. The advent of Raman microscopy, still scarcely used for biological samples, allowed chemical characterization of cellular inclusions in vivo. Using this method, herein we provide a substantial revision of the cellular crystalline inclusions across the broad diversity of eukaryotes examining all major supergroups. Surprisingly, here we show that 80 % of these crystalline inclusions contain purines, mostly anhydrous guanine (62 %), guanine monohydrate (2 %), uric acid (12 %) and xanthine (4 %). Hence, our findings indicate that purine biocrystallization is a very general and an ancestral eukaryotic process operating by an as-yet-unknown mechanism. Purine crystalline inclusions are high-capacity and rapid-turnover reserves of nitrogen of a great metabolic importance, as well as optically active elements, e.g., present in the light sensing eyespots of flagellates, possessing even more hypothetical functions. Thus, we anticipate our work to be a starting point for more in-depth studies of this phenomenon on the detailed level spanning from cell biology to global ecology, with further potential applications in biotechnologies, bio-optics or in human medicine.

microbiology↗

bioRxiv2017

Statistical methods for large ensemble of super-resolution stochastic single particle trajectories

Following recent progresses in super-resolution microscopy obtained in the last decade, massive amount of redundant single stochastic trajectories are now available for statistical analysis. Flows of trajectories of molecules or proteins are sampling the cell membrane or its interior at a very high time and space resolution. Several statistical analysis were developed to extract information contained in these data, such as the biophysical parameters of the underlying stochastic motion to reveal the cellular organization. These trajectories can further reveal hidden subcellular organization. We present here the statistical analysis of these trajectories based on the classical Langevin equation, which serves as a model of trajectories. Parametric and non-parametric estimators are constructed by discretizing the stochastic equations and they allow recovering tethering forces, diffusion tensor or membrane organization from measured trajectories, that differ from physical ones by a localization noise. Modeling, data analysis and automatic detection algorithms serve extracting novel biophysical features such as potential wells and other sub-structures, such as rings at an unprecedented spatiotem-poral resolution. It is also possible to reconstruct the surface membrane of a biological cell from the statistics of projected random trajectories.

biophysics↗

bioRxiv2023

DNA-origami line-actants control domain organisation and fission in synthetic membranes

Cells can precisely program the shape and lateral organisation of their membranes using protein machinery. Aiming to replicate a comparable degree of control, here we introduce DNA-Origami Line-Actants (DOLAs) as synthetic analogues of membrane-sculpting proteins. DOLAs are designed to selectively accumulate at the line-interface between co-existing domains in phase-separated lipid membranes, modulating the tendency of the domains to coalesce. With experiments and coarse-grained simulations, we demonstrate that DOLAs can reversibly stabilise two-dimensional analogues of Pickering emulsions on synthetic giant liposomes, enabling dynamic programming of membrane lateral organisation. The control afforded over membrane structure by DOLAs extends to three-dimensional morphology, as exemplified by a proof-of-concept synthetic pathway leading to vesicle fission. With DOLAs we lay the foundations for mimicking, in synthetic systems, some of the critical membrane-hosted functionalities of biological cells, including signalling, trafficking, sensing, and division.

biophysics↗

bioRxiv2020

The C-terminal actin binding domain of talin forms an asymmetric catch bond with F-actin

Focal adhesions (FAs) are large, integrin-based adhesion complexes that link cells to the extracellular matrix (ECM). Previous work demonstrates that FAs form only when and where they are necessary to transmit force between the cellular cytoskeleton and the ECM, but how this occurs remains poorly understood. Talin is a 270 kDa adapter protein that links integrins to filamentous (F)-actin and recruits additional components during FA assembly in a force-dependent manner. Cell biological and developmental data demonstrate that the third, and C-terminal, F-actin binding site (ABS3) of talin is required for normal FA formation. However, ABS3 binds F-actin only weakly in in vitro, biochemical assays. We used a single-molecule optical trap assay to examine how and whether ABS3 binds F-actin under physiologically relevant, pN mechanical loads. We find that ABS3 forms a directional catch bond with F-actin when force is applied towards the pointed end of the actin filament, with binding lifetimes more than 100-fold longer than when force is applied towards the barbed end. Long-lived bonds to F-actin under load require the ABS3 C-terminal dimerization domain, whose cleavage is known to regulate focal adhesion turnover. Our results support a mechanism in which talin ABS3 preferentially binds and orients actin filaments with barbed ends facing the cell periphery, thus nucleating long-range order in the actin cytoskeleton. We suggest that talin ABS3 may function as a molecular AND gate that allows FA growth only when sufficient integrin density, F-actin polarization, and mechanical tension are simultaneously present.

biophysics↗

bioRxiv2022

A Caenorhabditis elegans nck-1 and filamentous actin-regulating protein pathway mediates a key cellular defense against bacterial pore-forming proteins

Pore-forming proteins (PFPs) comprise the largest single class of bacterial protein virulence factors and are expressed by many human and animal bacterial pathogens. Cells that are attacked by these virulence factors activate epithelial intrinsic cellular defenses (or INCEDs) to prevent the attendant cellular damage, cellular dysfunction, osmotic lysis, and organismal death. Several conserved PFP INCEDs have been identified using the nematode Caenorhabditis elegans and the nematicidal PFP Cry5B, including mitogen-activated protein kinase (MAPK) signaling pathways. Here we demonstrate that the gene nck-1, which has homologs from Drosophila to humans and links cell signaling with localized F-actin polymerization, is required for INCED against small-pore PFPs in C. elegans. Reduction/loss of nck-1 function results in C. elegans hypersensitivity to PFP attack, a hallmark of a gene required for INCEDs against PFPs. This requirement for nck-1-mediated INCED functions cell-autonomously in the intestine and is specific to PFPs but not other tested stresses. Genetic interaction experiments indicate that nck-1-mediated INCED against PFP attack is independent of the major MAPK PFP INCED pathways. Proteomics and cell biological and genetic studies further indicate that nck-1 functions with F-actin cytoskeleton modifying genes like arp2/3, erm-1, and dbn-1 and that nck-1/arp2/3 promote pore repair at the membrane surface and protect against PFP attack independent of p38 MAPK. Consistent with these findings, PFP attack causes significant changes in the amount of actin cytoskeletal proteins and in total amounts of F-actin in the target tissue, the intestine. nck-1 mutant animals appear to have lower F-actin levels than wild-type C. elegans. Studies on nck-1 and other F-actin regulating proteins have uncovered a new and important role of this pathway and the actin cytoskeleton in PFP INCED and protecting an intestinal epithelium in vivo against PFP attack. Author SummaryThe mechanism of action for a significant number of bacterial protein toxins is the formation of pores in the membrane of target cells. Host cells contain programmed defenses against such attacks. Here we use the model system of the roundworm Caenorhabditis elegans and crystal proteins produced by Bacillus thuringiensis to demonstrate a new defense pathway mediated by the activity of the NCK-1 protein. Consistent with its known function in mammalian cells, the NCK-1-mediated defense involves various actin-interacting proteins and affects the kinetics of pore repair. This pathway is novel in its independence from MAPK signaling. Furthermore, the NCK-1 activity is found to be generally needed for defense against multiple pore-forming proteins and yet is specific to defense against such proteins but not against other environmental stressors.

microbiology↗

bioRxiv2024

Modular Fluorescent Cholesterol Naphthalimide Probes And Their Application For Cholesterol Trafficking Studies In Cells

Development of fluorescent cholesterol analogs to better understand subcellular cholesterol trafficking is of great interest for cell biology and medicine. Our approach utilizes a bifunctional 1,8-naphthalimide scaffold with a push-pull character, modified on one side with a head group and a linker on the other side connecting it to cholesterol via an ester bond. Through structure-function studies, weve explored how different substituents--linkers and head groups--affect the ability of these fluorescent cholesterol naphthalimide analogs (CNDs) to mimic natural cholesterol behavior at both molecular and cellular levels. We categorized the resulting analogs into three groups: neutral, charged, and those featuring a hydroxyl group. Each compound was assessed for its solvatochromic behavior in organic solvents and model membranes. Extensive all-atom molecular dynamics simulations helped us examine how these analogs perform in model membranes compared to cholesterol. Additionally, we investigated the partitioning of these fluorescent probes in phase-separated giant unilamellar vesicles. We evaluated the uptake and distribution of these probes within mouse fibroblast cells and astrocytes, for their subcellular distributions in lysosomes and compared that to BODIPY-cholesterol, a well-regarded fluorescent cholesterol analog. The internalization efficiency of the fluorescent probes varies in different cell types and is affected mainly by the head groups. Our results demonstrate that the modular design significantly simplifies the creation of fluorescent cholesterol probes bearing distinct spectral, biophysical, and cellular targeting features, which makes it a valuable toolkit for the investigation of subcellular distribution and trafficking of cholesterol and its derivatives.

biochemistry↗

bioRxiv2019

Excitation of Faraday-like body waves in vibrated living earthworms

Biological cells and many living organisms are mostly made of liquids and therefore, by analogy with liquid drops, they should exhibit a range of fundamental nonlinear phenomena such as the onset of standing surface waves. Here, we test four common species of earthworm to demonstrate that vertical vibration of living worms lying horizontally of a flat solid surface results in the onset of subharmonic Faraday-like body waves, which is possible because earthworms have a hydrostatic skeleton with a flexible skin and a liquid-filled body cavity. Our findings are supported by theoretical analysis based on a model of parametrically excited vibrations in liquid-filled elastic cylinders using material parameters of the worms body reported in the literature. The ability to excite nonlinear subharmonic body waves in a living organism could be used to probe, and potentially to control, important biophysical processes such as the propagation of nerve impulses, thereby opening up avenues for addressing biological questions of fundamental impact.

biophysics↗

bioRxiv2023

Integrated high-confidence and high-throughput approaches for quantifying synapse engulfment by oligodendrocyte precursor cells

Oligodendrocyte precursor cells (OPCs) sculpt neural circuits through the phagocytic engulfment of synapses during development and in adulthood. However, precise techniques for analyzing synapse engulfment by OPCs are limited. Here, we describe a two-pronged cell biological approach for quantifying synapse engulfment by OPCs which merges low-and high-throughput methodologies. In the first method, an adeno-associated virus encoding a pH-sensitive, fluorescently-tagged synaptic marker is expressed in neurons in vivo. This construct allows for the differential labeling of presynaptic inputs that are contained outside of and within acidic phagolysosomal compartments. When followed by immunostaining for markers of OPCs and synapses in lightly fixed tissue, this approach enables the quantification of synapses engulfed by around 30-50 OPCs within a given experiment. In the second method, OPCs isolated from dissociated brain tissue are fixed, incubated with fluorescent antibodies against presynaptic proteins, and then analyzed by flow cytometry. This approach enables the quantification of presynaptic material within tens of thousands of OPCs in less than one week. These methods extend beyond the current imaging-based engulfment assays designed to quantify synaptic phagocytosis by brain-resident immune cells, microglia. Through the integration of these methods, the engulfment of synapses by OPCs can be rigorously quantified at both the individual and populational levels. With minor modifications, these approaches can be adapted to study synaptic phagocytosis by numerous glial cell types in the brain.

neuroscience↗

bioRxiv2019

Repertoire of morphable proteins in an organism

All living organisms have evolved to contain a set of proteins with variable physical and chemical properties. Efforts in the field of structural biology have contributed to uncovering the shape and the variability of each component. A set of experimental coordinates for a given protein can be used to define the \"morphness/unmorphness\". Here we show the results of global analysis of more than a thousand E. coli proteins, demonstrating that it would be a comprehensive method of understanding the evolved repertoire in an organism. By collecting \"UnMorphness Factor\" (UMF) determined for each of the proteins, the lowest and the highest boundaries of the experimentally observable structural variation are understood. The distribution of UMFs obtained for an organism is expected to represent how rigid and flexible components are balanced. The present analysis extends to evaluate the growing data from single particle cryo-electron microscopy, providing valuable information on effective interpretation to structural changes of proteins and the supramolecular complexes. The data and the method presented here also conform to FAIR data principles, having potential significance to advance the field of structural and molecular cell biology.

biophysics↗