Syntaxin clusters and cholesterol affect the mobility of Syntaxin1a
Biophys J. 2024 Jan 13:S0006-3495(24)00028-6. doi: 10.1016/j.bpj.2024.01.012. Online ahead of print.ABSTRACTSyntaxin1a (Syx1a) is essential for stimulated exocytosis in neuroendocrine cells. The vesicle docking process involves the formation of nanoscale Syx1a domains on the plasma membrane and the Syx1a clusters disintegrate during the fusion process. Syx1a nanodomains are static yet Syx1a molecules dynamically enter and leave the domains; the process by which these clusters maintain this balance is unclear. In this work, the dynamics of the Syx1a molecules is elucidated relative to the cluster position through a labeling...
Source: Biophysical Journal - January 15, 2024 Category: Physics Authors: Alan W Weisgerber Zden ěk Otruba Michelle K Knowles Source Type: research
An intracellular hydrophobic nexus critical for hERG1 channel slow deactivation
Biophys J. 2024 Jan 12:S0006-3495(24)00026-2. doi: 10.1016/j.bpj.2024.01.010. Online ahead of print.ABSTRACTSlow deactivation is a critical property of voltage-gated K+ channels encoded by the human Ether-à-go-go-Related Gene 1 (hERG). hERG1 channel deactivation is modulated by interactions between intracellular N-terminal Per-Arnt-Sim (PAS) and C-terminal cyclic nucleotide-binding homology (CNBh) domains. The PAS domain is multipartite, comprising a globular domain (gPAS; residues 26-135) and an N-terminal PAS-cap that is further subdivided into an initial unstructured "tip" (residues 1-12) and an amphipathic α-helical ...
Source: Biophysical Journal - January 14, 2024 Category: Physics Authors: Whitney A Stevens-Sostre Lisandra Flores-Aldama Daniel Bustos Jin Li Jo ão H Morais-Cabral Lucie Delemotte Gail A Robertson Source Type: research
Statistical analysis of the autocorrelation function in fluorescence correlation spectroscopy
Biophys J. 2024 Jan 12:S0006-3495(24)00027-4. doi: 10.1016/j.bpj.2024.01.011. Online ahead of print.ABSTRACTFluorescence correlation spectroscopy (FCS) is a powerful method to measure concentration, mobility, and stoichiometry in solution and in living cells, but quantitative analysis of FCS data remains challenging due to the correlated noise in the autocorrelation function (ACF) of FCS. We demonstrate here that least-squares fitting of the conventional ACF is incompatible with the χ2 goodness-of-fit test and systematically underestimates the true fit parameter uncertainty. To overcome this challenge, a simple method to ...
Source: Biophysical Journal - January 14, 2024 Category: Physics Authors: John Kohler Kwang-Ho Hur Joachim Dieter Mueller Source Type: research
Membranes get in shape: Biophysics of curving bilayers
Biophys J. 2024 Feb 6;123(3):273-276. doi: 10.1016/j.bpj.2024.01.004. Epub 2024 Jan 13.ABSTRACTMembrane curvature is ubiquitous and essential in cell biology. Curved membranes have several distinct features, including specific protein and lipid sorting, distinct lipid ordering, and changes in transbilayer stress. Curvature also interplays with membrane tension to generate forces that change membrane shape. This research highlight summarizes recent contributions to this topic published in Biophysical Journal.PMID:38219739 | DOI:10.1016/j.bpj.2024.01.004 (Source: Biophysical Journal)
Source: Biophysical Journal - January 14, 2024 Category: Physics Authors: Carolyn R Shurer Kandice R Levental Source Type: research
Force balance ratio is a robust predictor of arterial thrombus stability
Biophys J. 2024 Jan 10:S0006-3495(24)00010-9. doi: 10.1016/j.bpj.2024.01.009. Online ahead of print.ABSTRACTThrombus formation on a damaged vessel wall can lead to the formation of a stable occlusive/subocclusive clot or unstable embolizing thrombus. Both outcomes can cause significant health damage. The mechanisms that regulate maximum thrombus size, its stability, and embolization in both micro- and macrocirculation are poorly understood. To investigate the impact of flow and intrathrombus forces on the stability of homogeneous and heterogeneous platelet thrombi in a wide range of thrombus geometries, critical interplate...
Source: Biophysical Journal - January 11, 2024 Category: Physics Authors: Efim S Bershadsky Daniel A Ermokhin Vladimir A Kurattsev Mikhail A Panteleev Dmitry Y Nechipurenko Source Type: research
An accurate probabilistic step finder for time-series analysis
Biophys J. 2024 Jan 9:S0006-3495(24)00009-2. doi: 10.1016/j.bpj.2024.01.008. Online ahead of print.ABSTRACTNoisy time-series data-from various experiments, including Förster resonance energy transfer, patch clamp, and force spectroscopy, among others-are commonly analyzed with either hidden Markov models or step-finding algorithms, both of which detect discrete transitions. Hidden Markov models, including their extensions to infinite state spaces, inherently assume exponential-or technically geometric-holding time distributions, biasing step locations toward steps with geometric holding times, especially in sparse and/or ...
Source: Biophysical Journal - January 11, 2024 Category: Physics Authors: Alex Rojewski Max Schweiger Ioannis Sgouralis Matthew Comstock Steve Press é Source Type: research
On the possibility of engineering social evolution in microfluidic environments
Biophys J. 2024 Feb 6;123(3):407-419. doi: 10.1016/j.bpj.2024.01.007. Epub 2024 Jan 9.ABSTRACTMany species of microbes cooperate by producing public goods from which they collectively benefit. However, these populations are under the risk of being taken over by cheating mutants that do not contribute to the pool of public goods. Here we present theoretical findings that address how the social evolution of microbes can be manipulated by external perturbations to inhibit or promote the fixation of cheaters. To control social evolution, we determine the effects of fluid-dynamical properties such as flow rate or domain geometr...
Source: Biophysical Journal - January 11, 2024 Category: Physics Authors: Gurdip Uppal Dervis Can Vural Source Type: research
Molecular dynamics simulations of HIV-1 matrix-membrane interactions at different stages of viral maturation
Biophys J. 2024 Feb 6;123(3):389-406. doi: 10.1016/j.bpj.2024.01.006. Epub 2024 Jan 9.ABSTRACTAlthough the structural rearrangement of the membrane-bound matrix (MA) protein trimers upon HIV-1 maturation has been reported, the consequences of MA maturation on the MA-lipid interactions are not well understood. Long-timescale molecular dynamics simulations of the MA multimeric assemblies of immature and mature virus particles with our realistic asymmetric membrane model have explored MA-lipid interactions and lateral organization of lipids around MA complexes. The number of stable MA-phosphatidylserine and MA-phosphatidylino...
Source: Biophysical Journal - January 10, 2024 Category: Physics Authors: Puja Banerjee Kun Qu John A G Briggs Gregory A Voth Source Type: research
Single-molecule FRET probes allosteric effects on protein-translocating pore loops of a AAA+ machine
Biophys J. 2024 Feb 6;123(3):374-388. doi: 10.1016/j.bpj.2024.01.002. Epub 2024 Jan 9.ABSTRACTAAA+ proteins (ATPases associated with various cellular activities) comprise a family of powerful ring-shaped ATP-dependent translocases that carry out numerous vital substrate-remodeling functions. ClpB is a AAA+ protein disaggregation machine that forms a two-tiered hexameric ring, with flexible pore loops protruding into its center and binding to substrate proteins. It remains unknown whether these pore loops contribute only passively to substrate-protein threading or have a more active role. Recently, we have applied single-mo...
Source: Biophysical Journal - January 10, 2024 Category: Physics Authors: Marija Iljina Hisham Mazal Ashan Dayananda Zhaocheng Zhang George Stan Inbal Riven Gilad Haran Source Type: research
Anomalous Coarsening of Coalescing Nucleoli in Human Cells
Biophys J. 2024 Jan 8:S0006-3495(24)00006-7. doi: 10.1016/j.bpj.2024.01.005. Online ahead of print.ABSTRACTCoarsening is a ubiquitous phenomenon in droplet systems near thermodynamic equilibrium - as an increase in droplet size lowers the system's free energy - however, coarsening of droplets in non-equilibrium systems, such as the cell nucleus, is far from understood. Liquid condensates in the cell nucleus, like nucleoli, form by liquid-liquid phase separation and play a key role in the nuclear organization. In human cells, nucleolar droplets are nucleated at the beginning of the cell cycle and coarsen with time by coales...
Source: Biophysical Journal - January 9, 2024 Category: Physics Authors: Giorgi Arsenadze Christina M Caragine Taylor Coakley Iraj Eshghi Yuwei Yang Alex Wofford Alexandra Zidovska Source Type: research
Anomalous Coarsening of Coalescing Nucleoli in Human Cells
Biophys J. 2024 Jan 8:S0006-3495(24)00006-7. doi: 10.1016/j.bpj.2024.01.005. Online ahead of print.ABSTRACTCoarsening is a ubiquitous phenomenon in droplet systems near thermodynamic equilibrium - as an increase in droplet size lowers the system's free energy - however, coarsening of droplets in non-equilibrium systems, such as the cell nucleus, is far from understood. Liquid condensates in the cell nucleus, like nucleoli, form by liquid-liquid phase separation and play a key role in the nuclear organization. In human cells, nucleolar droplets are nucleated at the beginning of the cell cycle and coarsen with time by coales...
Source: Biophysical Journal - January 9, 2024 Category: Physics Authors: Giorgi Arsenadze Christina M Caragine Taylor Coakley Iraj Eshghi Yuwei Yang Alex Wofford Alexandra Zidovska Source Type: research
Dynamics of receptor activation by agonists
Biophys J. 2024 Jan 4:S0006-3495(24)00003-1. doi: 10.1016/j.bpj.2024.01.003. Online ahead of print.ABSTRACTHow do agonists turn on receptors? The model system we have used to address this question is the adult-type skeletal muscle nicotinic acetylcholine receptor (AChR). This ligand-gated ion channel has 2 orthosteric sites (for neurotransmitters) in the extracellular domain linked to an allosteric site (a gate) in the transmembrane domain. The goal of this Perspective is to summarize how measurements of agonist binding energy reveal the dynamics of the neurotransmitter sites and the fundamental link between binding and ga...
Source: Biophysical Journal - January 5, 2024 Category: Physics Authors: Anthony Auerbach Source Type: research
Phosphomimetic substitutions in TDP-43's transiently α-helical region suppress phase separation
Biophys J. 2024 Jan 4:S0006-3495(24)00001-8. doi: 10.1016/j.bpj.2024.01.001. Online ahead of print.ABSTRACTPhosphorylated TAR DNA-binding protein of 43 kDa (TDP-43) is present within the aggregates of several age-related neurodegenerative disorders, such as amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD) and Alzheimer's disease, to the point that the presence of phosphorylated TDP-43 is considered a hallmark of some of these diseases. The majority of known TDP-43 phosphorylation sites detected in ALS/FTLD patients is located in the low complexity domain (LCD), the same domain that has been sho...
Source: Biophysical Journal - January 5, 2024 Category: Physics Authors: Raza Haider Srinivasa Penumutchu Solomiia Boyko Witold K Surewicz Source Type: research
Dynamics of receptor activation by agonists
Biophys J. 2024 Jan 4:S0006-3495(24)00003-1. doi: 10.1016/j.bpj.2024.01.003. Online ahead of print.ABSTRACTHow do agonists turn on receptors? The model system we have used to address this question is the adult-type skeletal muscle nicotinic acetylcholine receptor (AChR). This ligand-gated ion channel has 2 orthosteric sites (for neurotransmitters) in the extracellular domain linked to an allosteric site (a gate) in the transmembrane domain. The goal of this Perspective is to summarize how measurements of agonist binding energy reveal the dynamics of the neurotransmitter sites and the fundamental link between binding and ga...
Source: Biophysical Journal - January 5, 2024 Category: Physics Authors: Anthony Auerbach Source Type: research
Phosphomimetic substitutions in TDP-43's transiently α-helical region suppress phase separation
Biophys J. 2024 Jan 4:S0006-3495(24)00001-8. doi: 10.1016/j.bpj.2024.01.001. Online ahead of print.ABSTRACTPhosphorylated TAR DNA-binding protein of 43 kDa (TDP-43) is present within the aggregates of several age-related neurodegenerative disorders, such as amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD) and Alzheimer's disease, to the point that the presence of phosphorylated TDP-43 is considered a hallmark of some of these diseases. The majority of known TDP-43 phosphorylation sites detected in ALS/FTLD patients is located in the low complexity domain (LCD), the same domain that has been sho...
Source: Biophysical Journal - January 5, 2024 Category: Physics Authors: Raza Haider Srinivasa Penumutchu Solomiia Boyko Witold K Surewicz Source Type: research
