Top 10 Biorxiv Papers Today in Biophysics


2.069 Mikeys
#1. Organization and Regulation of Chromatin by Liquid-Liquid Phase Separation
Bryan A Gibson, Lynda K Doolittle, Liv E Jensen, Nathan Gamarra, Sy Redding, Michael K Rosen
Genomic DNA is highly compacted in the nucleus of eukaryotic cells as a nucleoprotein assembly called chromatin. The basic unit of chromatin is the nucleosome, where ~146 base pair increments of the genome are wrapped and compacted around the core histone proteins. Further genomic organization and compaction occur through higher order assembly of nucleosomes. This organization regulates many nuclear processes, and is controlled in part by histone post-transtranslational modifications and chromatin-binding proteins. Mechanisms that regulate the assembly and compaction of the genome remain unclear. Here we show that in the presence of physiologic concentrations of mono- and divalent salts, histone tail-driven interactions drive liquid-liquid phase separation (LLPS) of nucleosome arrays, resulting in substantial condensation. Phase separation of nucleosomal arrays is inhibited by histone acetylation, whereas histone H1 promotes phase separation, further compaction, and decreased dynamics within droplets, mirroring the relationship...
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biorxivpreprint: Organization and Regulation of Chromatin by Liquid-Liquid Phase Separation https://t.co/r3CBulIYs9 #bioRxiv
Alexis_Verger: #365papers 1⃣7⃣ Organization and Regulation of Chromatin by Liquid-Liquid Phase Separation https://t.co/WXFfUeJCqu https://t.co/VEvuLRi6SO
ShorterLab: Organization and Regulation of Chromatin by Liquid-Liquid Phase Separation, very exciting work from Mike Rosen et al.!: https://t.co/v1LC8mwi8r
YSPTSPS: This paper from the lab of Michael "Oh My Goodness" Rosen is as exciting and simple and elegant and impactful as you can read. A monument to the continued utility of biochemistry even the age of omics and super-scopes (which I also love, obviously). https://t.co/QmP9tAvjM9
biorxiv_biophys: Organization and Regulation of Chromatin by Liquid-Liquid Phase Separation https://t.co/owlLq4rYBT #biorxiv_biophys
ReddingLab: Preprint from our collab with Michael Rosen UTSW and @bryangibsonphd is now live! Organization and Regulation of Chromatin by Liquid-Liquid Phase Separation https://t.co/wpUfLyw0CB
Castaneda_lab: And the transcription/gene regulation/phase separation story gets even more interesting. See the preprint linked below from Rosen's lab. https://t.co/rt4TGg5g4K
YSPTSPS: Organization and Regulation of Chromatin by Liquid-Liquid Phase Separation https://t.co/QmP9tAvjM9
PromPreprint: Organization and Regulation of Chromatin by Liquid-Liquid Phase Separation https://t.co/bNtVjpXWat
rassobar: https://t.co/ZH7EIFmqCW
bryangibsonphd: Check it interwebs!, up on @biorxivpreprint now is our collab with the @ReddingLab on liquid-liquid phase separation of the #chromatin fiber. Dynamic and reversible compaction and material properties modulation through #phaseseparation. https://t.co/cUzQJOzAhL
skurukuti: https://t.co/BZMeND3Jpi
Alexis_Lomakin: RT @biorxiv_biophys: Organization and Regulation of Chromatin by Liquid-Liquid Phase Separation https://t.co/owlLq4rYBT #biorxiv_biophys
meter: RT @biorxiv_biophys: Organization and Regulation of Chromatin by Liquid-Liquid Phase Separation https://t.co/owlLq4rYBT #biorxiv_biophys
rraadd88: RT @biorxiv_biophys: Organization and Regulation of Chromatin by Liquid-Liquid Phase Separation https://t.co/owlLq4rYBT #biorxiv_biophys
Parikki: RT @YSPTSPS: Organization and Regulation of Chromatin by Liquid-Liquid Phase Separation https://t.co/QmP9tAvjM9
Ryan_Cupo: RT @biorxiv_biophys: Organization and Regulation of Chromatin by Liquid-Liquid Phase Separation https://t.co/owlLq4rYBT #biorxiv_biophys
PeterLyLab: RT @biorxivpreprint: Organization and Regulation of Chromatin by Liquid-Liquid Phase Separation https://t.co/r3CBulIYs9 #bioRxiv
lab_zhang: RT @YSPTSPS: Organization and Regulation of Chromatin by Liquid-Liquid Phase Separation https://t.co/QmP9tAvjM9
biofiziksmama: RT @biorxiv_biophys: Organization and Regulation of Chromatin by Liquid-Liquid Phase Separation https://t.co/owlLq4rYBT #biorxiv_biophys
oz__gur: RT @biorxivpreprint: Organization and Regulation of Chromatin by Liquid-Liquid Phase Separation https://t.co/r3CBulIYs9 #bioRxiv
LabZhu: RT @YSPTSPS: Organization and Regulation of Chromatin by Liquid-Liquid Phase Separation https://t.co/QmP9tAvjM9
AlZuko1: RT @biorxiv_biophys: Organization and Regulation of Chromatin by Liquid-Liquid Phase Separation https://t.co/owlLq4rYBT #biorxiv_biophys
krishna92: RT @biorxiv_biophys: Organization and Regulation of Chromatin by Liquid-Liquid Phase Separation https://t.co/owlLq4rYBT #biorxiv_biophys
NZthRzXeiplAQA6: RT @biorxivpreprint: Organization and Regulation of Chromatin by Liquid-Liquid Phase Separation https://t.co/r3CBulIYs9 #bioRxiv
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Authors: 6
Total Words: 5350
Unqiue Words: 1835

2.015 Mikeys
#2. A DNA-based voltmeter for organelles
Anand Saminathan, John Devany, Kavya S Pillai, Aneesh Tazhe Veetil, Michael Schwake, Yamuna Krishnan
The role of membrane potential in most intracellular organelles remains unexplored because of the lack of suitable probes. We describe a DNA-based fluorescent reporter that quantitates membrane potential and can be targeted to specific organelles in live cells. It is equipped with a voltage sensitive fluorophore, a reference fluorophore for ratiometric quantification, and acts as an endocytic tracer. We could thereby measure the membrane potential of different intracellular organelles in living cells, which has not been possible previously. Our understanding of how membrane potential regulates organelle biology is poised to expand through the use of these new sensors.
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KrishnanYamuna: Presented our work below on a quantitative reporter for membrane potential in organelles. https://t.co/psdpyqNr0V Many organelles considered to have "0" membrane potential. We show the real values in inside live cells! :-) https://t.co/sYS1kMNfBm
anandsami999: Our latest work showing intracellular membrane containing ion channels and transporters similar to plasma membrane has non-zero membrane potential. Could voltage be a signaling cue in these compartments? Check it out! https://t.co/tm03xRItgp
madamscientist: RT @KrishnanYamuna: Presented our work below on a quantitative reporter for membrane potential in organelles. https://t.co/psdpyqNr0V Many…
analioj: RT @KrishnanYamuna: Presented our work below on a quantitative reporter for membrane potential in organelles. https://t.co/psdpyqNr0V Many…
sheeldodani: RT @KrishnanYamuna: Presented our work below on a quantitative reporter for membrane potential in organelles. https://t.co/psdpyqNr0V Many…
kwitschas: RT @KrishnanYamuna: Presented our work below on a quantitative reporter for membrane potential in organelles. https://t.co/psdpyqNr0V Many…
DrMichaelJBooth: RT @KrishnanYamuna: Presented our work below on a quantitative reporter for membrane potential in organelles. https://t.co/psdpyqNr0V Many…
GarciaSaez_Lab: RT @KrishnanYamuna: Presented our work below on a quantitative reporter for membrane potential in organelles. https://t.co/psdpyqNr0V Many…
balda_sanjeev: RT @KrishnanYamuna: Presented our work below on a quantitative reporter for membrane potential in organelles. https://t.co/psdpyqNr0V Many…
link_to_mk: RT @biorxivpreprint: A DNA-based voltmeter for organelles https://t.co/msGEPdx059 #bioRxiv
jani_maulik: RT @KrishnanYamuna: Presented our work below on a quantitative reporter for membrane potential in organelles. https://t.co/psdpyqNr0V Many…
Aneesh_UChicago: RT @KrishnanYamuna: Presented our work below on a quantitative reporter for membrane potential in organelles. https://t.co/psdpyqNr0V Many…
anandsami999: RT @KrishnanYamuna: Presented our work below on a quantitative reporter for membrane potential in organelles. https://t.co/psdpyqNr0V Many…
anandsami999: RT @biorxivpreprint: A DNA-based voltmeter for organelles https://t.co/msGEPdx059 #bioRxiv
KaHoLeung6: RT @KrishnanYamuna: Presented our work below on a quantitative reporter for membrane potential in organelles. https://t.co/psdpyqNr0V Many…
KaHoLeung6: RT @biorxivpreprint: A DNA-based voltmeter for organelles https://t.co/msGEPdx059 #bioRxiv
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Authors: 6
Total Words: 8439
Unqiue Words: 2576

2.01 Mikeys
#3. Direct synthesis of EM-visible gold nanoparticles on genetically encoded tags for single-molecule visualization in cells
Zhaodi Jiang, Xiumei Jin, Yuhua Li, Sitong Liu, Xiao-Man Liu, Yng-Ying Wang, Pei Zhao, Xinbin Cai, Ying Liu, Yaqi Tang, Xiaobin Sun, Yan Liu, Yanhong Hu, Ming Li, Gaihong Cai, Xiangbing Qi, She Chen, Li-Lin Du, Wanzhong He
Single-molecule visualization in cells with genetically encoded tags for electron microscopy (EM) has been a long-awaited but unimplemented tool for cell biologists. Here, we report an approach for directly synthesizing EM-visible gold nanoparticles (AuNPs) on cysteine-rich tags for single-molecule visualization in cells. We first uncovered an auto-nucleation suppression mechanism that allows specific synthesis of AuNPs on isolated cysteine-rich tags. We next exploited this mechanism to develop an approach for single-molecule detection of proteins in prokaryotic cells and achieved an unprecedented labeling efficiency. We then expanded it to more complicated eukaryotic cells and successfully detected the proteins targeted to various organelles, including the membranes of endoplasmic reticulum (ER) and nuclear envelope, ER lumen, nuclear pores, spindle pole bodies, and mitochondrial matrix. Thus, our implementation of genetically encoded tags for EM should allow cell biologists to address an enormous range of biological questions at...
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biorxivpreprint: Direct synthesis of EM-visible gold nanoparticles on genetically encoded tags for single-molecule visualization in cells https://t.co/NoxLnTHFHu #bioRxiv
biorxiv_biophys: Direct synthesis of EM-visible gold nanoparticles on genetically encoded tags for single-molecule visualization in cells https://t.co/c2FQDNSdZ8 #biorxiv_biophys
danengw: Such genetically encoded tags for gold particles can have many applications in electron tomography and cell biology. https://t.co/vCtRzpzgiO
jeff_j_lange: This is such a cool paper! Direct synthesis of nascent gold nanoparticles directly onto proteins of interest in intact cells without the need for antibodies! https://t.co/EW7gsSeBuB
thallium81: Might be neat to try to look at localization of low abundant proteins ? https://t.co/L6iudWU7IM
PromPreprint: Direct synthesis of EM-visible gold nanoparticles on genetically encoded tags for single-molecule visualization in cells https://t.co/6xkmk7BId2
Montibeller_GG: Direct synthesis of EM-visible gold nanoparticles on genetically encoded tags for single-molecule visualization in cells https://t.co/28ZJimUthx
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Sample Sizes : [76, 76, 94, 64]
Authors: 19
Total Words: 24583
Unqiue Words: 4467

2.004 Mikeys
#4. Nanoscopic Stoichiometry and Single-Molecule Counting
Daniel Nino, Daniel Djayakarsana, Joshua N Milstein
Single-molecule localization microscopy (SMLM) has the potential to revolutionize proteomic and genomic analyses by providing information on the number and stoichiometry of proteins or nucleic acids aggregating at spatial scales below the diffraction limit of light. Here we present a method for molecular counting with SMLM built upon the exponentially distributed blinking statistics of photoswitchable fluorophores, with a focus on organic dyes. We provide a practical guide to molecular counting, highlighting many of the challenges and pitfalls, by benchmarking the method on fluorescently labeled, surface mounted DNA origami grids. The accuracy of the results illustrates SMLM's utility for optical '-omics' analysis.
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MilsteinLab: A preprint of our newest paper on #SMLM molecular counting with photoswitchable dyes is available. Great work by an excellent graduate student Daniel Nino applying #superresolution #microscopy to #Genomics and #Proteomics https://t.co/3ojnAEpuSJ
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Authors: 3
Total Words: 0
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2.001 Mikeys
#5. The HCN Channel Voltage Sensor Undergoes A Large Downward Motion During Hyperpolarization
Gucan Dai, Teresa K. Aman, Frank DiMaio, William N. Zagotta
Voltage-gated ion channels (VGICs) underlie almost all electrical signaling in the body. They change their open probability in response to changes in transmembrane voltage, allowing permeant ions to flow across the cell membrane. Ion flow through VGICs underlies numerous physiological processes in excitable cells. In particular, hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which operate at the threshold of excitability, are essential for pacemaking activity, resting membrane potential, and synaptic integration. VGICs contain a series of positively-charged residues that are displaced in response to changes in transmembrane voltage, resulting in a conformational change that opens the pore. These voltage-sensing charges, which reside in the S4 transmembrane helix of the voltage-sensor domain (VSD) and within the membrane's electric field, are thought to move towards the inside of the cell (downwards) during membrane hyperpolarization. HCN channels are unique among VGICs because their open probability is...
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cryoEM_Papers: The HCN Channel Voltage Sensor Undergoes A Large Downward Motion During Hyperpolarization https://t.co/AtzrIDlxX1
AlexanderSobol6: The HCN Channel Voltage Sensor Undergoes A Large Downward Motion During Hyperpolarization https://t.co/tm9wYYWvLq
ProfSharona: RT @biorxiv_biophys: The HCN Channel Voltage Sensor Undergoes A Large Downward Motion During Hyperpolarization https://t.co/ZP2ifJg2WN #bi…
ProfSharona: RT @AlexanderSobol6: The HCN Channel Voltage Sensor Undergoes A Large Downward Motion During Hyperpolarization https://t.co/tm9wYYWvLq
osamaharraz: RT @AlexanderSobol6: The HCN Channel Voltage Sensor Undergoes A Large Downward Motion During Hyperpolarization https://t.co/tm9wYYWvLq
t2438: RT @cryoEM_Papers: The HCN Channel Voltage Sensor Undergoes A Large Downward Motion During Hyperpolarization https://t.co/AtzrIDlxX1
gqmartinez: RT @biorxiv_biophys: The HCN Channel Voltage Sensor Undergoes A Large Downward Motion During Hyperpolarization https://t.co/ZP2ifJg2WN #bi…
GomisCarolina: RT @biorxiv_biophys: The HCN Channel Voltage Sensor Undergoes A Large Downward Motion During Hyperpolarization https://t.co/ZP2ifJg2WN #bi…
shatanikm: RT @cryoEM_Papers: The HCN Channel Voltage Sensor Undergoes A Large Downward Motion During Hyperpolarization https://t.co/AtzrIDlxX1
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Authors: 4
Total Words: 10595
Unqiue Words: 2604

1.998 Mikeys
#6. Computational modeling reveals frequency modulation of calcium-cAMP/PKA pathway in dendritic spines
Donya Ohadi, Danielle L Schmitt, Barbara Calabrese, Shelley Halpain, Jin Zhang, Padmini Rangamani
Dendritic spines are the primary excitatory postsynaptic sites which act as subcompartments of signaling. Calcium is often the first and rapid signal. Downstream of calcium, the cAMP/PKA pathway plays a critical role in the regulation of spine formation, morphological modifications, and ultimately, learning and memory. While the dynamics of calcium are reasonably well-studied, calcium-induced cAMP/PKA dynamics are not fully explored. In this study, we present a well-mixed model for the dynamics of calcium-induced cAMP/PKA dynamics in dendritic spines. The model is validated against experimental measurements in the literature. Further, we measure calcium dynamics in dendritic spines of cultured hippocampal CA1 neurons to justify the choice of model inputs. Our model predicts that the various steps in this pathway act as a frequency modulator for calcium and high frequency of calcium input is filtered by AC1 and PDEs in this pathway such that cAMP/PKA only responds to lower frequencies. This prediction has important implications for...
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Sample Sizes : [10]
Authors: 6
Total Words: 10994
Unqiue Words: 3052

1.998 Mikeys
#7. The GRASP domain in Golgi Reassembly and Stacking Proteins: differences and similarities between lower and higher Eukaryotes
Luis Felipe Mendes, Natalia Aparecida Fontana, Carolina Gimenes Oliveira, Marjorie Freire, Jose Lopes, Fernando Melo, Antonio J Costa-Filho
The Golgi complex is part of the endomembrane system and is responsible for receiving transport cargos from the endoplasmic reticulum and for sorting and targeting them to their final destination. To perform its function in higher eukaryotic cells, the Golgi needs to be correctly assembled as a flatted membrane sandwich kept together by a protein matrix. The correct mechanism controlling the Golgi cisternae assembly is not yet known, but it is already accepted that the Golgi Reassembly and Stacking Protein (GRASP) is a main component of the Golgi protein matrix. Unlike mammalian cells, which have two GRASP genes, lower eukaryotes present only one gene and distinct Golgi cisternae assembly. In this study, we performed a set of biophysical studies to get insights on both human GRASP55 and GRASP65 and compare them with GRASPs from lower eukaryotes (S. cerevisiae and C. neoformans). Our data suggest that both human GRASPs are essentially different from each other and GRASP65 is more similar to the subgroup of GRASPs from lower...
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biorxivpreprint: The GRASP domain in Golgi Reassembly and Stacking Proteins: differences and similarities between lower and higher Eukaryotes https://t.co/t3BsOQHJun #bioRxiv
biorxiv_biophys: The GRASP domain in Golgi Reassembly and Stacking Proteins: differences and similarities between lower and higher Eukaryotes https://t.co/IL1DZa1LHf #biorxiv_biophys
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Authors: 7
Total Words: 10129
Unqiue Words: 2974

1.998 Mikeys
#8. RPA phosphorylation regulates DNA resection
Michael M. Soniat, Logan R. Myler, Tanya T. Paull, Ilya J. Finkelstein
Genetic recombination in all kingdoms of life initiates when helicases and nucleases process (resect) the free DNA ends to expose single-stranded (ss) DNA overhangs. Resection termination in bacteria is programmed by a DNA sequence but the mechanisms limiting resection in eukaryotes have remained elusive. Using single-molecule imaging of reconstituted human DNA repair factors, we identify a general mechanism that limits DNA resection. BLM helicase together with EXO1 and DNA2 nucleases catalyze kilobase-length DNA resection on nucleosome-coated DNA. The resulting ssDNA is rapidly bound by RPA, which is in turn phosphorylated as part of the DNA damage response (DDR). Remarkably, phosphorylated RPA (pRPA) inhibits DNA resection via regulation of BLM helicase. pRPA suppresses BLM initiation at DNA ends and promotes the intrinsic helicase strand-switching activity. These findings establish that pRPA is a critical regulator of DNA repair enzymes and provides a feedback loop between the DDR and DNA resection termination.
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Sample Sizes : [50, 50, 50, 50, 50, 50, 60, 60, 60, 60, 60, 35, 90, 90, 80, 80, 80, 80, 7, 40, 50, 16, 15, 68, 68, 50, 40]
Authors: 4
Total Words: 10191
Unqiue Words: 3305

1.998 Mikeys
#9. An integrated microfluidic platform for quantifying drug permeation across biomimetic vesicle membranes
Michael Schaich, Jehangir Cama, Kareem Al Nahas, Diana Sobota, Kevin Jahnke, Siddharth Deshpande, Cees Dekker, Ulrich F Keyser
The low membrane permeability of candidate drug molecules is a major challenge in drug development and insufficient permeability is one reason for the failure of antibiotic treatment against bacteria. Quantifying drug transport across specific pathways in living systems is challenging since one typically lacks knowledge of the exact lipidome and proteome of the individual cells under investigation. Here, we quantify drug permeability across biomimetic liposome membranes, with comprehensive control over membrane composition. We integrate the microfluidic octanol-assisted liposome assembly platform with an optofluidic transport assay to create a complete microfluidic total analysis system for quantifying drug permeability. Our system enables us to form liposomes with charged lipids mimicking the negative charge of bacterial membranes at physiological salt and pH levels, which proved difficult with previous liposome formation techniques. Furthermore, the microfluidic technique yields an order of magnitude more liposomes per...
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cees_dekker: Now on @biorxivpreprint: An integrated microfluidic platform for quantifying drug permeation across biomimetic vesicle membranes https://t.co/PDn1p6Kc20 Great work by Keyser group @TheNanoporeSite, where we could also contribute a bit
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Sample Sizes : [10]
Authors: 8
Total Words: 6900
Unqiue Words: 2219

1.998 Mikeys
#10. Instantaneous polarized light imaging reveals activity dependent structural changes of dendrites in mouse hippocampal slices
Maki Koike-Tani, Takashi Tominaga, Rudolf Oldenbourg, Tomomi Tani
Intrinsic Optical Signal (IOS) imaging has been widely used to map patterns of brain activity in vivo in a label-free manner. Traditional IOS refers to changes in light transmission, absorption, and scattering, which have been correlated with neuronal swelling and volume changes in the observed tissue. Here we use polarized light for IOS imaging to monitor structural changes of cellular and sub-cellular architectures of neurons due to their synaptic activity in isolated brain slices. In order to reveal fast spatio-temporal changes of birefringence associated with neuronal activity, we developed the instantaneous PolScope. The instantaneous PolScope records changes in transmission, birefringence, and slow axis orientation in tissue at high spatial and temporal resolution using a single camera exposure. These capabilities enabled us to correlate polarization-sensitive IOS with traditional IOS on the same preparations. We detected reproducible spatio-temporal changes in both IOSs at the stratum radiatum in mouse hippocampal slices...
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Sample Sizes : [4590135, 8, 8, 8, 8, 30, 28, 7, 7, 7, 5, 5, 5, 7]
Authors: 4
Total Words: 13739
Unqiue Words: 3317

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