The Volume of Healthy Red Blood Cells is Optimal for Advective Oxygen Transport in Arterioles
This study explores, through high-fidelity numerical simulations, the impact of RBC volume on advectve oxygen transport efficiency through arterioles which form the area of greatest flow resistance in the circulatory system. The results show that, strikingly, RBCs with volumes similar to those found in vivo are most efficient to transport oxygen through arterioles. The flow resistance is related to the cell-free layer thickness, which is influenced by the shape and the motion of the RBCs: at low volumes RBCs deform and fold while at high volumes RBCs collide and follow more diffuse trajectories. In contrast, RBCs with a he...
Source: Biophysical Journal - April 20, 2024 Category: Physics Authors: Lucas Amoudruz Athena Economides Petros Koumoutsakos Source Type: research

The Volume of Healthy Red Blood Cells is Optimal for Advective Oxygen Transport in Arterioles
This study explores, through high-fidelity numerical simulations, the impact of RBC volume on advectve oxygen transport efficiency through arterioles which form the area of greatest flow resistance in the circulatory system. The results show that, strikingly, RBCs with volumes similar to those found in vivo are most efficient to transport oxygen through arterioles. The flow resistance is related to the cell-free layer thickness, which is influenced by the shape and the motion of the RBCs: at low volumes RBCs deform and fold while at high volumes RBCs collide and follow more diffuse trajectories. In contrast, RBCs with a he...
Source: Biophysical Journal - April 20, 2024 Category: Physics Authors: Lucas Amoudruz Athena Economides Petros Koumoutsakos Source Type: research

Transmembrane Determinants of Voltage Gating Differences Between BK (Slo1) and Slo3 Channels
This study investigates the molecular determinants that differentiate the voltage-gating properties of human Slo1 and mouse Slo3 channels. Utilizing Slo1/Slo3 chimeras, we pinpointed the selectivity filter region as a key factor in the Slo3 channel's reduced conductance at negative voltages. The S6 transmembrane (TM) segment was identified as pivotal for the Slo3 channel's biphasic deactivation kinetics at these voltages. Additionally, the S4 and S6 TM segments were found to be responsible for the gradual slope in the Slo3 channel's conductance-voltage (G-V) relationship, while multiple TM regions appear to be involved in ...
Source: Biophysical Journal - April 19, 2024 Category: Physics Authors: Qin Li Guanxing Chen Jiusheng Yan Source Type: research

Cell migration: Beyond Brownian motion
Biophys J. 2024 Apr 17:S0006-3495(24)00275-3. doi: 10.1016/j.bpj.2024.04.013. Online ahead of print.NO ABSTRACTPMID:38637988 | DOI:10.1016/j.bpj.2024.04.013 (Source: Biophysical Journal)
Source: Biophysical Journal - April 19, 2024 Category: Physics Authors: Rainer Klages Source Type: research

Kinetic cooperativity resolves bidirectional clogging within the nuclear pore complex
Biophys J. 2024 Apr 10:S0006-3495(24)00207-8. doi: 10.1016/j.bpj.2024.03.027. Online ahead of print.ABSTRACTAs the main gatekeeper of the nucleocytoplasmic transport in eukaryotic cells, the nuclear pore complex (NPC) faces the daunting task of facilitating the bidirectional transport of a high volume of macromolecular cargoes while ensuring the selectivity, speed, and efficiency of this process. The competition between opposing nuclear import and export fluxes passing through the same channel is expected to pose a major challenge to transport efficiency. It has been suggested that phase separation-like radial segregation ...
Source: Biophysical Journal - April 19, 2024 Category: Physics Authors: Tiantian Zheng Anton Zilman Source Type: research

A structure-based computational model of IP < sub > 3 < /sub > R1 incorporating Ca and IP3 regulation
In this study we present a coarse-grained model of IP3R1 which accounts for the channel architecture and the location of specific Ca and IP3 binding sites. This computational model accounts for the domain-domain interaction within and between the four subunits that form IP3R1, and also describes how ligand binding regulates these interactions. Using a kinetic model, we explore how two Ca binding sites on the cytosolic side of the channel interact with the IP3 binding site to regulate the channel open probability. Our primary finding is that the bell-shaped open probability of IP3R1 provides constraints on the relative stre...
Source: Biophysical Journal - April 17, 2024 Category: Physics Authors: D'Artagnan Greene Yohannes Shiferaw Source Type: research

A structure-based computational model of IP < sub > 3 < /sub > R1 incorporating Ca and IP3 regulation
In this study we present a coarse-grained model of IP3R1 which accounts for the channel architecture and the location of specific Ca and IP3 binding sites. This computational model accounts for the domain-domain interaction within and between the four subunits that form IP3R1, and also describes how ligand binding regulates these interactions. Using a kinetic model, we explore how two Ca binding sites on the cytosolic side of the channel interact with the IP3 binding site to regulate the channel open probability. Our primary finding is that the bell-shaped open probability of IP3R1 provides constraints on the relative stre...
Source: Biophysical Journal - April 17, 2024 Category: Physics Authors: D'Artagnan Greene Yohannes Shiferaw Source Type: research

A structure-based computational model of IP < sub > 3 < /sub > R1 incorporating Ca and IP3 regulation
In this study we present a coarse-grained model of IP3R1 which accounts for the channel architecture and the location of specific Ca and IP3 binding sites. This computational model accounts for the domain-domain interaction within and between the four subunits that form IP3R1, and also describes how ligand binding regulates these interactions. Using a kinetic model, we explore how two Ca binding sites on the cytosolic side of the channel interact with the IP3 binding site to regulate the channel open probability. Our primary finding is that the bell-shaped open probability of IP3R1 provides constraints on the relative stre...
Source: Biophysical Journal - April 17, 2024 Category: Physics Authors: D'Artagnan Greene Yohannes Shiferaw Source Type: research

DNA and mRNA as molecular speed bumps in Escherichia coli's cytoplasm
Biophys J. 2024 Apr 13:S0006-3495(24)00274-1. doi: 10.1016/j.bpj.2024.04.012. Online ahead of print.NO ABSTRACTPMID:38616488 | DOI:10.1016/j.bpj.2024.04.012 (Source: Biophysical Journal)
Source: Biophysical Journal - April 15, 2024 Category: Physics Authors: Arnold J Boersma Source Type: research

DNA and mRNA as molecular speed bumps in Escherichia coli's cytoplasm
Biophys J. 2024 Apr 13:S0006-3495(24)00274-1. doi: 10.1016/j.bpj.2024.04.012. Online ahead of print.NO ABSTRACTPMID:38616488 | DOI:10.1016/j.bpj.2024.04.012 (Source: Biophysical Journal)
Source: Biophysical Journal - April 15, 2024 Category: Physics Authors: Arnold J Boersma Source Type: research

Characteristic Fingerprint Spectrum of α-Synuclein Mutants on Terahertz Time-Domain Spectroscopy
CONCLUSION: The SNCA wild-type protein and two mutant variants (A30P and A53T) had distinct characteristic fingerprint spectra on THz time-domain spectroscopy. This novel label-free detection method has great potential for the differential diagnosis of Parkinson's disease subtypes.PMID:38615192 | DOI:10.1016/j.bpj.2024.04.011 (Source: Biophysical Journal)
Source: Biophysical Journal - April 14, 2024 Category: Physics Authors: Xiaofang Zhao Chenlong Yang Xin Chen Yu Sun Weihai Liu Qinggang Ge Jun Yang Source Type: research

Map Conformational Landscapes of Intrinsically Disordered Proteins with Polymer Physics Quantities
Biophys J. 2024 Apr 12:S0006-3495(24)00272-8. doi: 10.1016/j.bpj.2024.04.010. Online ahead of print.ABSTRACTDisordered proteins are conformationally flexible proteins that are biologically important and have been implicated in devastating diseases such as Alzheimer's and cancer. Unlike stably-folded structured proteins, disordered proteins sample a range of different conformations that needs to be accounted for. Here, we treat disordered proteins as polymer chains, and compute a dimensionless quantity called instantaneous shape ratio (Rs), as Rs = Ree2/Rg2, where Ree is end-to-end distance and Rg is radius of gyration. Ext...
Source: Biophysical Journal - April 14, 2024 Category: Physics Authors: Hossain Shadman Jesse D Ziebarth Caleb E Gallops Ray Luo Zhengxin Li Hai-Feng Chen Yongmei Wang Source Type: research

Optimizing properties of translocation-enhancing transmembrane proteins
In this study, we demonstrate that specific properties of transmembrane proteins/peptides can enhance membrane permeation of amphiphilic peptides. Using coarse-grained molecular dynamics with free energy calculations, we identify key translocation-enhancing attributes of transmembrane proteins/peptides: a continuous hydrophilic patch, charged residues preferably in the membrane center, and aromatic hydrophobic residues. By employing both coarse-grained and atomistic simulations, complemented by experimental validation, we show that these properties not only enhance peptide translocation but also speed up lipid flip-flop. T...
Source: Biophysical Journal - April 14, 2024 Category: Physics Authors: Ladislav Barto š Martina Drabinov á Robert V ácha Source Type: research

Characteristic Fingerprint Spectrum of α-Synuclein Mutants on Terahertz Time-Domain Spectroscopy
CONCLUSION: The SNCA wild-type protein and two mutant variants (A30P and A53T) had distinct characteristic fingerprint spectra on THz time-domain spectroscopy. This novel label-free detection method has great potential for the differential diagnosis of Parkinson's disease subtypes.PMID:38615192 | DOI:10.1016/j.bpj.2024.04.011 (Source: Biophysical Journal)
Source: Biophysical Journal - April 14, 2024 Category: Physics Authors: Xiaofang Zhao Chenlong Yang Xin Chen Yu Sun Weihai Liu Qinggang Ge Jun Yang Source Type: research

Map Conformational Landscapes of Intrinsically Disordered Proteins with Polymer Physics Quantities
Biophys J. 2024 Apr 12:S0006-3495(24)00272-8. doi: 10.1016/j.bpj.2024.04.010. Online ahead of print.ABSTRACTDisordered proteins are conformationally flexible proteins that are biologically important and have been implicated in devastating diseases such as Alzheimer's and cancer. Unlike stably-folded structured proteins, disordered proteins sample a range of different conformations that needs to be accounted for. Here, we treat disordered proteins as polymer chains, and compute a dimensionless quantity called instantaneous shape ratio (Rs), as Rs = Ree2/Rg2, where Ree is end-to-end distance and Rg is radius of gyration. Ext...
Source: Biophysical Journal - April 14, 2024 Category: Physics Authors: Hossain Shadman Jesse D Ziebarth Caleb E Gallops Ray Luo Zhengxin Li Hai-Feng Chen Yongmei Wang Source Type: research