Biophysical journal最新文献_第6页

Auditory cellular cooperativity probed via spontaneous otoacoustic emissions.

IF 3.2 3区生物学

Biophysical journal Pub Date : 2025-03-03 DOI: 10.1016/j.bpj.2025.02.023

Christopher Bergevin, Rebecca E Whiley, Hero Wit, Geoffrey A Manley, Pim van Dijk

{"title":"Auditory cellular cooperativity probed via spontaneous otoacoustic emissions.","authors":"Christopher Bergevin, Rebecca E Whiley, Hero Wit, Geoffrey A Manley, Pim van Dijk","doi":"10.1016/j.bpj.2025.02.023","DOIUrl":"10.1016/j.bpj.2025.02.023","url":null,"abstract":"As a sound pressure detector that uses energy to boost both its sensitivity and selectivity, the inner ear is an active nonequilibrium system. The collective processes of the inner ear that give rise to this exquisite functionality remain poorly understood. One manifestation of the active ear across the animal kingdom is the presence of spontaneous otoacoustic emission (SOAE), idiosyncratic arrays of spectral peaks that can be measured using a sensitive microphone in the ear canal. Current SOAE models attempt to explain how multiple peaks arise, and generally assume a spatially distributed tonotopic system. However, the nature of the generators, their coupling, and the role of noise (e.g., Brownian motion) are hotly debated, especially given the inner ear morphological diversity across vertebrates. One means of probing these facets of emission generation is studying fluctuations in SOAE peak properties, which produce amplitude and frequency modulations (AM and FM, respectively). These properties are likely related to the presence of noise affecting active cellular generation elements, and the coupling between generators. To better biophysically constrain models, this study characterizes the fluctuations in filtered SOAE peak waveforms, focusing on interrelations within and across peaks. A systematic approach is taken, examining three species that exhibit disparate inner ear morphologies: humans, barn owls, and green anole lizards. To varying degrees across all three groups, SOAE peaks have intrapeak (IrP) and interpeak (IPP) correlations indicative of interactions between generative elements. Activity from anole lizards, whose auditory sensory organ is relatively much smaller than that of humans or barn owls, showed a much higher incidence of nearest-neighbor IPP correlations. We propose that these data reveal characteristics of SOAE cellular generators acting cooperatively, allowing the ear to function as an optimized detector.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Morphological trapping of neurotransmitters in synaptic clefts: A new dimension in neural plasticity.

IF 3.2 3区生物学

Biophysical journal Pub Date : 2025-02-28 DOI: 10.1016/j.bpj.2025.02.026

Bugra Kaytanli, Mattia Bacca

引用次数: 0

Further exploration of the quantitative distance-energy and contact number-energy relationships for predicting the binding affinity of protein-ligand complexes.

IF 3.2 3区生物学

Biophysical journal Pub Date : 2025-02-27 DOI: 10.1016/j.bpj.2025.02.021

Yong Xiao Yang, Bao Ting Zhu

{"title":"Further exploration of the quantitative distance-energy and contact number-energy relationships for predicting the binding affinity of protein-ligand complexes.","authors":"Yong Xiao Yang, Bao Ting Zhu","doi":"10.1016/j.bpj.2025.02.021","DOIUrl":"10.1016/j.bpj.2025.02.021","url":null,"abstract":"Accurate estimation of the strength of the protein-ligand interaction is important in the field of drug discovery. The binding strength can be determined by using experimental binding affinity assays which are both time and labor consuming and costly. Predicting the binding affinity/energy in silico is an alternative approach, particularly for virtual screening of large data sets. In general, the distance-based terms such as electrostatic and van der Waals interactions are among the key determinants of binding energy. In this work, the distance-binding energy relationships, i.e., E ∝ -d-k, are further explored, extended, and developed for protein-ligand binding affinity prediction. The contributions of different atom-type pairs were considered synthetically and jointly. Additionally, the contact number-energy relationships (E ∝ -nk) were also explored for protein-ligand binding affinity prediction. Significantly, the power exponents of the distances or contact numbers in the energy functions are not restricted by the existing theories concerning van der Waals and electrostatic energies (expressed as ar6-br12 and cr). The performances of the new distance-based or contact number-based models are better than the performances of those sophisticated non-machine-learning-based scoring functions developed before. The exploration and extension of the distance-energy and contact number-energy relationships may offer insights into the development of more effective methods for predicting the protein-ligand binding affinity accurately and analyzing the protein-ligand interactions rationally.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sphingomyelin slows interfacial hydrogen-bonding dynamics in lipid membranes.

IF 3.2 3区生物学

Biophysical journal Pub Date : 2025-02-26 DOI: 10.1016/j.bpj.2025.02.020

Cong Xu, James E Fitzgerald, Edward Lyman, Carlos R Baiz

{"title":"Sphingomyelin slows interfacial hydrogen-bonding dynamics in lipid membranes.","authors":"Cong Xu, James E Fitzgerald, Edward Lyman, Carlos R Baiz","doi":"10.1016/j.bpj.2025.02.020","DOIUrl":"10.1016/j.bpj.2025.02.020","url":null,"abstract":"Interfacial hydrogen bonding (H-bonding) partly determines membrane structure, heterogeneity, and dynamics. Given the chemical diversity of lipids, it is important to understand how composition determines lipid-lipid interactions and how those are translated to H-bond populations and dynamics. Here, we investigate the role of palmitoyl sphingosylphosphorylcholine (PSM) in modulating lipid H-bond networks in combination with dipalmitoyl phosphatidylcholine (DPPC) using ultrafast two-dimensional infrared (2D IR) spectroscopy and molecular dynamics simulations. We report composition-dependent H-bond ensembles for ester and amide carbonyls, with increased H-bond populations and slower dynamics with higher PSM concentrations. Specifically, amide carbonyl 2D IR spectra indicate that PSM, acting as an H-bond donor, partially replaces water-mediated interactions, with the number of direct lipid-lipid H-bonds constituting up to 20% of the total. These interactions create comparatively stable H-bond networks that significantly slow interfacial dynamics. 2D IR spectra show an H-bond lifetime slowdown of 45% in an equimolar mixture of the two lipids compared to DPPC alone. This study highlights PSM's dual role in H-bonding, which increases membrane viscosity and stabilizes lipid interfaces, providing molecular insights into the role of sphingolipids in cell membranes. The findings further emphasize the synergy of experimental and computational approaches for extracting molecular-level insights into interfacial lipid-lipid and lipid-water interactions in heterogeneous membranes.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cellular teamwork in cancer invasion.

IF 3.2 3区生物学

Biophysical journal Pub Date : 2025-02-26 DOI: 10.1016/j.bpj.2025.02.024

Guhan Qian, Paolo P Provenzano

引用次数: 0

Diverse toxins exhibit a common binding mode to the nicotinic acetylcholine receptors.

IF 3.2 3区生物学

Biophysical journal Pub Date : 2025-02-26 DOI: 10.1016/j.bpj.2025.02.022

Hung N Do, Jessica Z Kubicek-Sutherland, S Gnanakaran

{"title":"Diverse toxins exhibit a common binding mode to the nicotinic acetylcholine receptors.","authors":"Hung N Do, Jessica Z Kubicek-Sutherland, S Gnanakaran","doi":"10.1016/j.bpj.2025.02.022","DOIUrl":"10.1016/j.bpj.2025.02.022","url":null,"abstract":"Nicotinic acetylcholine receptors (nAChRs) are critical ligand-gated ion channels in the human nervous system. They are targets for various neurotoxins produced by algae, plants, and animals. While many structures of nAChRs bound by neurotoxins have been published, the binding mechanism of toxins to the nAChRs remains unclear. In this work, we have performed extensive Gaussian accelerated molecular dynamics simulations on several Aplysia californica nAChRs in complex with α-conotoxins, strychnine, and pinnatoxins, as well as human nAChRs in complex with α-bungarotoxin and α-conotoxin, to determine the binding and dissociation pathways of the toxins to the nAChRs and the associated effects. We uncovered two common binding and dissociation pathways shared by toxins and nAChRs. In the first binding pathway, the toxins diffused from the bulk solvent to bind a region near the extracellular pore before moving downwards along the nAChRs to the nAChR orthosteric pocket. The second binding pathway involved a direct diffusion of the toxins from the bulk solvent into the nAChR orthosteric pocket. The dissociation pathways were the reverse of the observed binding pathways. Notably, we determined that the electrostatically bipolar interactions between the nAChR orthosteric pocket and toxins provided an explanation for the common binding mode shared by diverse toxins.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Quality control maps: Real-time quantitative control of single-molecule localization microscopy data.

IF 3.2 3区生物学

Biophysical journal Pub Date : 2025-02-25 DOI: 10.1016/j.bpj.2025.02.018

Sébastien Mailfert, Meriem Djendli, Roxane Fabre, Didier Marguet, Nicolas Bertaux

{"title":"Quality control maps: Real-time quantitative control of single-molecule localization microscopy data.","authors":"Sébastien Mailfert, Meriem Djendli, Roxane Fabre, Didier Marguet, Nicolas Bertaux","doi":"10.1016/j.bpj.2025.02.018","DOIUrl":"10.1016/j.bpj.2025.02.018","url":null,"abstract":"Single-molecule localization microscopy (SMLM) has revolutionized the understanding of cellular organization by reconstructing informative images with quantifiable spatial distributions of molecules far beyond the optical diffraction limit. Much effort has been devoted to optimizing localization accuracy. One such approach is the assessment of SMLM data quality in real time rather than after lengthy postacquisition analysis, which nevertheless represents a computational challenge We overcame this difficulty by implementing an innovative mathematical approach we designed to drastically reduce the computational analysis of particle localization. Our quality control maps (QCM) workflow enables a much higher rate of data processing compared to that limited by the frequency required by current cameras. Accordingly, using an innovative computational approach for the detection step and an estimator based on a Gaussian model of the point spread function, subpixel particle locations and their accuracy can be determined through a straightforward analytical calculation without the need for iterations. As a true parameter-free algorithm, QCM is robust and adaptable to all types of SMLM data, with high speed enabling the real-time calculation of quantitative quality control indicators. Such features are compatible with smart microscopy, the concept of which depends on the adjustment of acquisition parameters in real time according to analytical results. Finally, the offline QCM mode can be used as a tool to evaluate synthetic or previously acquired data, as well as to teach the basic concepts of SMLM.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Vesicle docking and fusion pore modulation by the neuronal calcium sensor Synaptotagmin-1.

IF 3.2 3区生物学

Biophysical journal Pub Date : 2025-02-25 DOI: 10.1016/j.bpj.2025.02.013

Maria Tsemperouli, Sudheer Kumar Cheppali, Felix Rivera-Molina, David Chetrit, Ane Landajuela, Derek Toomre, Erdem Karatekin

引用次数: 0

Cooperativity of PIP2 and PS lipids modulates PH domain binding.

IF 3.2 3区生物学

Biophysical journal Pub Date : 2025-02-25 DOI: 10.1016/j.bpj.2025.02.019

Xiaobing Chen, Alfredo E Cardenas, Rose B Hudson, Ron Elber, Eric N Senning, Carlos R Baiz

{"title":"Cooperativity of PIP2 and PS lipids modulates PH domain binding.","authors":"Xiaobing Chen, Alfredo E Cardenas, Rose B Hudson, Ron Elber, Eric N Senning, Carlos R Baiz","doi":"10.1016/j.bpj.2025.02.019","DOIUrl":"10.1016/j.bpj.2025.02.019","url":null,"abstract":"Phosphatidylinositides constitute only 1%-3% of plasma membranes but play vital roles in cellular signaling. In particular, phosphatidylinositol 4,5-bisphosphate (PIP2) is involved in processes such as cytoskeleton organization and ion-channel regulation. Pleckstrin homology (PH) domains are modular domains found in many proteins and are known for their strong affinity for PIP2 headgroups. The role of lipid composition in PH domain binding to PIP2, particularly the inclusion of phosphatidylserine (PS), is not well understood. This study explores the mechanisms of PH domain binding to PIP2 using fluorescence spectroscopy, Fourier transform infrared spectroscopy, two-dimensional infrared spectroscopy, and molecular dynamics simulations. We find that anionic PIP2 and PS alter the interfacial environment compared to phosphatidylcholines. Additionally, the PH domain promotes the localization of anionic lipid domains upon binding. Our results highlight the role of PS in lipid domain formation within membranes and its potential influence on protein binding affinities and lipid geometries. Specifically, we discovered a strong interaction between PIP2 and PS whereby hydrogen bonding within these anionic lipids drives localization in the membrane. This interaction also regulates protein binding at the membrane interface. Our findings suggest that cooperativity between PIP2 and PS is key to the formation of localized lipid domains and the recruitment of proteins such as the PH domain of phospholipase C-δ1.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ergosterol depletion by fish AMP analogs likely enhances fungal membrane permeability.

IF 3.2 3区生物学

Biophysical journal Pub Date : 2025-02-25 DOI: 10.1016/j.bpj.2025.02.015

Samuel Cashman-Kadri, Ismail Fliss, Lucie Beaulieu, Patrick Lagüe

{"title":"Ergosterol depletion by fish AMP analogs likely enhances fungal membrane permeability.","authors":"Samuel Cashman-Kadri, Ismail Fliss, Lucie Beaulieu, Patrick Lagüe","doi":"10.1016/j.bpj.2025.02.015","DOIUrl":"10.1016/j.bpj.2025.02.015","url":null,"abstract":"The molecular interactions between a fungal membrane model and SJGAP, a 32-amino-acid antimicrobial peptide (AMP) derived from skipjack tuna GAPDH, as well as four analogs, were investigated using molecular dynamics simulations and Fourier transform infrared (FTIR) spectroscopy. In a previous study, Analog 7, modified by replacing three alanine residues with leucine residues, exhibited unique antifungal activity without any antibacterial effect. This contrasts with other analogs, which showed both antifungal and antibacterial effects. In this study, Analog 7 displayed the strongest interactions with the membrane's hydrophobic core, inserting more deeply and causing significantly greater membrane deformation and thinning compared with the other analogs. Its presence caused significant membrane deformation, evident from the displacement of both the phosphate groups and terminal methyls of the lipids. Notably, Analog 7 was the only analog to induce a marked depletion of ergosterol around the peptide insertion site. FTIR spectroscopy experiments further confirmed the distinctive impact of Analog 7 on a fungal membrane model. The combined results from molecular dynamics simulations and spectroscopy emphasize the critical role of leucine substitutions in Analog 7, particularly at residues 18 and 19 within the central α helix, in promoting membrane thinning and inducing ergosterol depletion, suggesting increased membrane permeabilization, which could explain its previously reported antifungal specificity. This study provides the first insights into the molecular interactions between a GAPDH-derived AMP and a fungal membrane model, offering valuable information about its antifungal mechanism of action.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143498671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0