Biophysical journal最新文献

{"title":"Mapping single-cell rheology of ascidian embryos in the cleavage stages using AFM.","authors":"Takahiro Kotani, Tomohiro Matsuo, Megumi Yokobori, Yosuke Tsuboyama, Yuki Miyata, Yuki Fujii, Kaori Kuribayashi-Shigetomi, Takaharu Okajima","doi":"10.1016/j.bpj.2025.06.038","DOIUrl":"10.1016/j.bpj.2025.06.038","url":null,"abstract":"<p><p>During early embryo development, cell division is highly organized and synchronized. Understanding the mechanical properties of embryonic cells as a material is crucial in elucidating the physical mechanism underlying embryogenesis. Previous studies on developing embryos using atomic force microscopy (AFM) revealed that single cells of ascidian embryos in the cleavage stage stiffened and softened during cell division. However, how embryonic cells, as a compliant material, exhibit viscoelastic properties during the cell cycle remains poorly characterized. In this study, we investigated the rheological properties of embryonic cells in the animal hemisphere in the cleavage stages using stress-relaxation AFM and approach-retraction force curve AFM techniques. The AFM measurements revealed that developing single cells followed a power-law rheology observed in single-cell rheology in vitro. The embryonic cells increased the modulus (stiffness) and decreased the fluidity (the power-law exponent) toward cell division. We found three rheological states in developing embryos during the cell cycle. The correlation between the cell modulus and the fluidity during the cell cycle was collapsed onto a master curve with a negative correlation, indicating that embryonic cells tightly interacting with the neighboring cells conserved the universality of rheological behavior observed in single cells in vitro.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551850","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}

{"title":"Challenges and Lessons Learned in Attempts to Develop In Vitro Models for Ultrasound Neuromodulation using Local Field Potential Measurements in Hippocampal Tissue.","authors":"Martin Loynaz Prieto,Daniel V Madison,Merritt Maduke","doi":"10.1016/j.bpj.2025.06.039","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.06.039","url":null,"abstract":"Ultrasound neuromodulation is a rapidly developing tool for non-invasive control of brain activity. An in vitro model recapitulating the effects of ultrasound on neural tissue in vivo would be extremely valuable in guiding the development of this tool for optimal implementation. Yet, there are relatively few studies of ultrasound on neural activity in vitro. Here we describe our attempts to measure neuromodulatory outcomes using local field potential measurements in two in vitro models of hippocampal activity. First, we measured the effects of ultrasound at 1 MHz and 100-600 kPa on a rat hippocampal in vitro model of sharp wave ripples. Our primary protocol involved brief ultrasound pulses delivered at intervals shorter than the mean interval between sharp wave ripple events, with other stimulus protocols tested with small sample size. No set of parameters produced detectable effects on the amplitude or frequency of sharp wave ripples. We considered whether missing synaptic connections or the relatively small volume in brain slices might account for the lack of effect in our experimental setup. To test these hypotheses, and to examine ultrasound's effects in another system, we measured the effects of ultrasound on theta oscillations in the intact mouse hippocampus in vitro. We found that ultrasound at 1 MHz and 500 kPa, applied continuously for 2 seconds, produced no detectable effects on the amplitude or frequency of in vitro theta oscillations. Finally, we considered a novel mechanism for ultrasound's effects on neural activity, in which acoustic pressure causes microscale phase transitions in the pores of ion channels, such as nicotinic receptor channels, that exhibit hydrophobic gating. To test this hypothesis, we repeated our experiments on the intact hippocampus in the presence of 5 μM nicotine; however, as with the other experimental systems, we found no detectable effects of ultrasound in our experimental set-up.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"36 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144533356","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}

{"title":"Activation of Visual Rhodopsin Probed by Single-Shot Transient IR Spectroscopy","authors":"Luiz Schubert, Franz Bartl, Joachim Heberle","doi":"10.1016/j.bpj.2025.06.030","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.06.030","url":null,"abstract":"In order to understand the structure-function relationships of proteins, it is important to study their dynamics under physiological conditions. The advent of X-ray free electron lasers has made it possible to obtain the three-dimensional structures of proteins and their reaction intermediates at room temperature. However, these experiments are very demanding and require extensive planning. Here, we demonstrate that time-resolved infrared difference spectroscopy using quantum cascade lasers is a powerful tool for studying the dynamics of protein conformational changes. This method complements structural biology experiments and aids in data interpretation. We demonstrate the feasibility of studying the irreversible photoreaction of the G-protein-coupled receptor rhodopsin using single shots.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"103 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504025","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}

{"title":"ATP directly modulates thick filament structure and function in porcine myocardium","authors":"Marcus Rhodehamel, Meihua Guo, Vivek P. Jani, Hailey Flannagan, Shengyao Yuan, Maicon Landim-Vieira, Weikang Ma","doi":"10.1016/j.bpj.2025.06.037","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.06.037","url":null,"abstract":"Cardiac contraction is achieved through cyclic cross-bridge interactions between overlapping myosin-containing thick filaments and actin-containing thin filaments. This process is powered by ATP hydrolysis by myosin which must be sufficient for maintaining cardiac output. Myocardial ATP concentration is tightly maintained via several mechanisms. However, in decompensated end-stage heart failure, these mechanisms fail, resulting in depressed myocardial ATP levels, impaired cross-bridge kinetics, and reduced cardiac output. Here we tested the hypothesis that ATP has a direct effect on thick filament activation by subjecting permeabilized porcine myocardium to increasing concentrations of ATP. Small-angle X-ray diffraction showed that higher ATP concentrations caused a structural transition in myosin heads from quasi-helically ordered OFF states, where they are held in close proximity to the thick filament backbone, to disordered ON states where they are free to move closer to thin filaments. Mechanically, high ATP did not alter maximum calcium-activated tension, though increasing ATP right shifted the tension vs. calciumCa<ce:sup loc=\"post\">2+</ce:sup> curve and accelerated both myosin attachment and detachment rates, consistent with prior studies. Power output and maximum unloaded shortening velocity also significantly increased with increased ATP concentration. Together our structural and functional results indicate that ATP can directly turn thick filaments ON in porcine myocardium, suggest a potential mechanism for the excessive proportion of myosin in the inactivated state in certain heart diseases. The profound effect on cross-bridge kinetics also suggests that reduced ATP concentration impairs relaxation and may also play a role in diastolic dysfunction.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"2 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504024","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}

{"title":"The effects of bicarbonate on the aberrant photon response in murine rod photoreceptors","authors":"Clint L. Makino, Md Shahabe Uddin Talukder, Brianna Kim, Rajan D. Adhikari, Heidi E. Hamm, Vsevolod V. Gurevich, Colin Klaus, Giovanni Caruso","doi":"10.1016/j.bpj.2025.06.035","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.06.035","url":null,"abstract":"Retinal rod photoreceptors generate reproducible quantal responses enabling them to \"count\" single photons. Interestingly, in mammalian rods, one photoisomerization in several hundred elicits an aberrant response that is larger than normal and persists for a variable period lasting up to tens of seconds. Although rare, aberrant responses influence signaling because many rods converge onto downstream neurons and because \"normal\" and aberrant single photon responses temporally summate in steady light. Bicarbonate increases the normal photon response and the maximal response of rods, but its effect on the aberrant responses is not known. To find out, we used a fully space-resolved, biophysical model of visual transduction in the murine rod and corroborated the results with <ce:italic>ex vivo</ce:italic> electroretinogram (ERG) recordings. In our simulations, the increased circulating current with bicarbonate raised [Ca<ce:sup loc=\"post\">2+</ce:sup>]<ce:inf loc=\"post\">in</ce:inf>, which suppressed the shutoff of photoexcited rhodopsin during the normal single photon response but not during the aberrant response. Consequently, the normal single photon response was enlarged to a greater extent than the aberrant response. In ERG recordings, aberrant responses gave rise to a long-lived tail in the bright flash response, that was used to assess how they were affected by bicarbonate. Indeed, the increase in aberrant response amplitude with bicarbonate was less than that for the normal photon response, consistent with modeling. In simulations, the accumulation of aberrant responses produced a slow, secondary rise in the step response to subsaturating intensities. But in the ERG, the secondary rise seemed to disappear with bicarbonate. By boosting normal photon responses and the maximal response, bicarbonate elicited a droop in the step response due to light adaptation (not included in the model) that was more prominent and appeared at lower intensities. Because bicarbonate also reduced the relative contribution of the aberrant response component, the droop merged with and obscured the secondary rise.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"45 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504028","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}

{"title":"Allosteric coupling between a lipid bilayer and a membrane protein","authors":"Clarisse Fourel, Yanna Gautier, Alexandre Pozza, François Giraud, Elodie Point, Christel Le Bon, Karine Moncoq, Guillaume Stirnemann, Jérôme Hénin, Ewen Lescop, Laurent J. Catoire","doi":"10.1016/j.bpj.2025.06.033","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.06.033","url":null,"abstract":"Biological membranes are complex environments whose functions are closely tied to the dynamic interactions between lipids and proteins. Here, we utilize high-pressure NMR of lipid nanodiscs paired with molecular dynamics simulations to elucidate at the atomic scale the allosteric dialog between the lipid bilayer and a model membrane protein, OmpX. We discover that OmpX delays the gelation process by liquefying the annular shell of lipids through hydrophobic and roughness matching processes at the protein surface. Furthermore, modification of the mechanical properties of the lipid bilayer directly impacts the energy landscape of amino acid side chains at the lipid/protein interface but also unexpectedly at the protein core. Our work highlights a thermodynamically coupled but kinetically uncoupled allosteric pathway linking lipid dynamics with the interior of membrane proteins, directly impacting our understanding of membrane function.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"54 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504027","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}

{"title":"Information Theory Optimization of Signals from Small Angle Scattering Measurements","authors":"Robert P. Rambo, John A. Tainer","doi":"10.1016/j.bpj.2025.06.031","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.06.031","url":null,"abstract":"Small angle X-ray scattering (SAXS) of particles in solution informs on the conformational states and assemblies of biological macromolecules (bioSAXS) outside of cryo- and solid-state conditions. In bioSAXS, the SAXS measurement under dilute conditions, is resolution-limited and through an inverse Fourier transform, the measured SAXS intensities directly relates to the physical space occupied by the particles via the <ce:italic>P</ce:italic>(<ce:italic>r</ce:italic>)-distribution. Yet, this inverse transform of SAXS data has been historically cast as an ill-posed, ill-conditioned problem requiring an indirect approach. Here, we show that through the applications of matrix and information theories, the inverse transform of SAXS intensity data is a well-conditioned problem. The so-called ill-conditioning of the inverse problem is directly related to the Shannon number. By exploiting the oversampling enabled by modern detectors, a direct inverse Fourier transform of the SAXS data is possible provided the recovered information does not exceed the Shannon number. The Shannon limit corresponds to the maximum number of significant singular values that can be recovered in a SAXS experiment suggesting this relationship is a fundamental property of band-limited inverse integral transform problems. This correspondence reduces the complexity of the inverse problem to the Shannon limit and maximum dimension. We propose a hybrid scoring function using an information theory framework that assesses both the quality of the model-data fit as well as the quality of the recovered <ce:italic>P</ce:italic>(<ce:italic>r</ce:italic>)-distribution. The hybrid score utilizes the Akaike Information Criteria and Durbin-Watson (<ce:italic>D</ce:italic><ce:inf loc=\"post\"><ce:italic>W</ce:italic></ce:inf>) statistic that considers parameter-model complexity, <ce:italic>i.e.</ce:italic>, degrees-of-freedom, and randomness of the model-data residuals. The described tests and findings extend the boundaries for bioSAXS by completing the information theory formalism initiated by Peter B. Moore to enable a quantitative measure of resolution in SAXS, robustly determine maximum dimension, and more precisely define the best paramater-model appropriately representing the observed scattering data.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"183 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144503828","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}

{"title":"Lipopolysaccharide nanoparticles, a biomimetic platform to study bacterial surface.","authors":"Massilia Abbas, Samantha Micciulla, Jean-Marie Teulon, Meriem Maalej, Macha Trembley, Roberta Marchetti, Antonio Molinaro, Michel Thépaut, Franck Fieschi, Jean-Luc Pellequer, Cédric Laguri","doi":"10.1016/j.bpj.2025.06.036","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.06.036","url":null,"abstract":"Lipopolysaccharides (LPS) are essential components of the outer membranes of Gram-negative bacteria, playing a crucial role in antimicrobial resistance, virulence, and the host’s immune response. Self-assembled particles displaying LPS are essential for biophysical studies addressing the behaviour of bacterial surfaces under specific biomimetic conditions. Styrene-maleic acid (SMA) copolymers were employed to form LPS nanoparticles, either from extracted LPS or directly from purified outer membranes. These nanoparticles, derived from pathogenic O157:H7 or laboratory <ce:italic>E. coli</ce:italic> strains, are well-defined in size and yield high-resolution nuclear magnetic resonance (NMR) spectra. They have been successfully used to investigate molecular recognition by a human C-type Lectin Receptor (CLR) of the immune system and interaction with polymyxin antibiotics using various biophysical methods. This study highlights the significance of LPS nanoparticles as bacterial surface mimetics and opens promising avenues for further research into LPS structure and interactions. The ability to generate well-defined LPS nanoparticles offers a powerful tool for studying the molecular mechanisms underlying bacterial pathogenesis and immune response.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"10 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504026","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}

{"title":"Inferring protein folding mechanisms from natural sequence diversity","authors":"Ezequiel A. Galpern, Ernesto A. Roman, Diego U. Ferreiro","doi":"10.1016/j.bpj.2025.06.034","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.06.034","url":null,"abstract":"Protein sequences serve as a natural record of the evolutionary constraints that shape their functional structures. We show that it is possible to use only sequence information to go beyond predicting native structures and global stability to infer the folding mechanisms of globular proteins. The one- and two-body evolutionary energy fields at the amino-acid level are mapped to a coarse-grained description of folding, where proteins are divided into contiguous folding elements, commonly referred to as foldons. For 15 diverse protein families, we calculated the folding mechanisms of hundreds of proteins by simulating an Ising chain of foldons, with their energetics determined by the amino acid sequences. We show that protein topology imposes limits on the variability of folding cooperativity within a family. While most beta and alpha/beta structures exhibit only a few possible mechanisms despite high sequence diversity, alpha topologies allow for diverse folding scenarios among family members. We show that both the stability and cooperativity changes induced by mutations can be computed directly using sequence-based evolutionary models.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"43 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144503829","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}

{"title":"A New Friend for Measuring Forces in Living Tissues.","authors":"William J Polacheck","doi":"10.1016/j.bpj.2025.06.028","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.06.028","url":null,"abstract":"","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"17 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488180","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}