Biophysical journal最新文献

{"title":"Temperature dependence of membrane viscosity of ternary lipid GUV with L_o domains.","authors":"Julia Tanaka, Kenya Haga, Naohito Urakami, Masayuki Imai, Yuka Sakuma","doi":"10.1016/j.bpj.2025.01.024","DOIUrl":"10.1016/j.bpj.2025.01.024","url":null,"abstract":"<p><p>In the cell membrane, it is considered that saturated lipids and cholesterol organize liquid-ordered (L_o) domains in a sea of liquid-disordered (L_d) phases and proteins relevant to cellular functions are localized in the L_o domains. Since the diffusion of transmembrane proteins is regulated by the membrane viscosity, we investigate the temperature dependence of the membrane viscosity of the ternary giant unilamellar vesicles (GUVs) composed of the saturated lipid 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, the unsaturated lipid 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), and cholesterol to understand the effect of the phase separation on the membrane viscosity using a microinjection technique. In the microinjection method, membrane viscosity is estimated by comparing the flow pattern induced on a spherical membrane with a hydrodynamic model. For phase-separated GUVs, the flow pattern is visualized by the motion of the domains. In this study, we developed a method to visualize the flow patterns of homogeneous GUVs above the phase separation temperature by using beads attached to the GUVs. We succeeded in measuring the membrane viscosity of ternary GUVs both above phase separation temperature and in the phase-separated region and found that the membrane viscosity decreases dramatically by phase separation. In the phase-separated region, i.e., GUVs with L_o domains, the membrane viscosity is determined by that of the L_d phase, η_Ld, and shows weak temperature dependence compared to that of the DOPC single-component GUV, which is a main component of the L_d phase. We revealed that the Moelwyn-Hughest model, which takes into account the effects of the membrane composition, viscosity of the pure component, and interaction between components, well describes the obtained membrane viscosity of the ternary GUV both above the phase separation temperature and in the phase-separated region. The drastic decrease of the membrane viscosity by the phase separation plays an important role in regulating the mobility of constituents in multi-component membranes.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"818-828"},"PeriodicalIF":3.2,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11897551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adhesion-driven vesicle translocation through membrane-covered pores.","authors":"Nishant Baruah, Jiarul Midya, Gerhard Gompper, Anil Kumar Dasanna, Thorsten Auth","doi":"10.1016/j.bpj.2025.01.012","DOIUrl":"10.1016/j.bpj.2025.01.012","url":null,"abstract":"<p><p>Translocation across barriers and through constrictions is a mechanism that is often used in vivo for transporting material between compartments. A specific example is apicomplexan parasites invading host cells through the tight junction that acts as a pore, and a similar barrier crossing is involved in drug delivery using lipid vesicles penetrating intact skin. Here, we use triangulated membranes and energy minimization to study the translocation of vesicles through pores with fixed radii. The vesicles bind to a lipid bilayer spanning the pore, the adhesion-energy gain drives the translocation, and the vesicle deformation induces an energy barrier. In addition, the deformation-energy cost for deforming the pore-spanning membrane hinders the translocation. Increasing the bending rigidity of the pore-spanning membrane and decreasing the pore size both increase the barrier height and shift the maximum to smaller fractions of translocated vesicle membrane. We compare the translocation of initially spherical vesicles with fixed membrane area and freely adjustable volume to that of initially prolate vesicles with fixed membrane area and volume. In the latter case, translocation can be entirely suppressed. Our predictions may help rationalize the invasion of apicomplexan parasites into host cells and design measures to combat the diseases they transmit.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"740-752"},"PeriodicalIF":3.2,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11897550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Positive feedback between RyR phosphorylation and Ca²⁺ leak promotes heterogeneous Ca²⁺ release.","authors":"Daisuke Sato, Bardia Ghayoumi, Anna Fasoli, Christopher Y Ko, Donald M Bers","doi":"10.1016/j.bpj.2025.01.023","DOIUrl":"10.1016/j.bpj.2025.01.023","url":null,"abstract":"<p><p>Structural heterogeneity in the distribution of ryanodine receptor (RyR) clusters in cardiac myocytes has been shown to have pro-arrhythmic effects. The presence of a mixture of large and small RyR clusters can potentiate arrhythmogenic calcium (Ca²⁺) waves. RyRs are subject to posttranslational modifications (PTMs), such as phosphorylation, that are linked to heart failure and other pathological conditions. This study aims to investigate how PTMs interact with the structural heterogeneity of RyR clusters and further increase heterogeneous Ca²⁺ release activities in cardiac myocytes. Using a physiologically detailed three-dimensional ventricular myocyte model containing approximately 2 million stochastic RyR channels, we simulated heterogeneous distributions of RyR clusters with and without PTMs. The results demonstrate that Ca²⁺ cycling and RyR phosphorylation by Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) create a positive feedback loop, which increases functional heterogeneity in the Ca²⁺ spark size distribution. In large clusters, the Ca²⁺ leak is substantial due to the large flux (number of channels recruited), leading to increased local Ca²⁺ concentrations, CaMKII activation, and further RyR sensitization, amplifying the leak. Conversely, in small clusters, the leak is limited, and sensitization is restricted. Furthermore, CaMKII activation can enhance late sodium (Na⁺) currents, increasing Na⁺ influx and subsequently raising Ca²⁺ levels via the Na⁺-Ca²⁺ exchanger, further promoting the Ca²⁺ leak and functional heterogeneity. We conclude that such positive feedback processes play a crucial role in arrhythmogenic Ca²⁺ wave initiation and propagation, particularly in heart failure myocytes, where PTMs are often dysregulated.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"717-721"},"PeriodicalIF":3.2,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11897541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Competing addition processes give distinct growth regimes in the assembly of 1D filaments.","authors":"Sk Ashif Akram, Tyler Brown, Stephen Whitelam, Georg Meisl, Tuomas P J Knowles, Jeremy D Schmit","doi":"10.1016/j.bpj.2025.01.018","DOIUrl":"10.1016/j.bpj.2025.01.018","url":null,"abstract":"<p><p>We present a model to describe the concentration-dependent growth of protein filaments. Our model contains two states, a low-entropy/high-affinity ordered state and a high-entropy/low-affinity disordered state. Consistent with experiments, our model shows a diffusion-limited linear growth regime at low concentration, followed by a concentration-independent plateau at intermediate concentrations, and rapid disordered precipitation at the highest concentrations. We show that growth in the linear and plateau regions is the result of two processes that compete amid the rapid binding and unbinding of nonspecific states. The first process is the addition of ordered molecules during periods in which the end of the filament is free of incorrectly bound molecules. The second process is the capture of defects, which occurs when consecutive ordered additions occur on top of incorrectly bound molecules. We show that a key molecular property is the probability that a diffusive collision results in a correctly bound state. Small values of this probability suppress the defect capture growth mode, resulting in a plateau in the growth rate when incorrectly bound molecules become common enough to poison ordered growth. We show that conditions that nonspecifically suppress or enhance intermolecular interactions, such as the addition of depletants or osmolytes, have opposite effects on the growth rate in the linear and plateau regimes. In the linear regime, stronger interactions promote growth by reducing dissolution events, but in the plateau regime stronger interactions inhibit growth by stabilizing incorrectly bound molecules.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"778-788"},"PeriodicalIF":3.2,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11897546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"β-Barrel proteins dictate the effect of core oligosaccharide composition on outer membrane mechanics.","authors":"Dylan R Fitzmaurice, Anthony Amador, Tahj Starr, Glen M Hocky, Enrique R Rojas","doi":"10.1016/j.bpj.2025.01.017","DOIUrl":"10.1016/j.bpj.2025.01.017","url":null,"abstract":"<p><p>The outer membrane is the defining structure of Gram-negative bacteria. We previously demonstrated that it is a major load-bearing component of the cell envelope and is therefore critical to the mechanical robustness of the bacterial cell. Here, to determine the key molecules and moieties within the outer membrane that underlie its contribution to cell envelope mechanics, we measured cell-envelope stiffness across several sets of mutants with altered outer-membrane sugar content, protein content, and electric charge. To decouple outer membrane stiffness from total cell envelope stiffness, we developed a novel microfluidics-based \"osmotic force-extension\" assay. In tandem, we developed a method to increase throughput of microfluidics experiments by performing them on color-coded pools of mutants. We found that truncating the core oligosaccharide, deleting the β-barrel protein OmpA, or deleting lipoprotein outer membrane-cell wall linkers all had the same modest, convergent effect on total cell-envelope stiffness in Escherichia coli. However, these mutations had large, variable effects on the ability of the cell wall to transfer tension to the outer membrane during large hyperosmotic shocks. Surprisingly, altering the electric charge of lipid A had little effect on the mechanical properties of the envelope. Finally, the presence or absence of OmpA determined whether truncating the core oligosaccharide decreased or increased envelope stiffness (respectively), revealing sign epistasis between these components. Based on these data we propose a putative structural model in which the spatial interactions between lipopolysaccharides, β-barrel proteins, and phospholipids coordinately determine cell envelope stiffness.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"765-777"},"PeriodicalIF":3.2,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11897544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Flipping the switch: Illuminating inverted ligand activation of peptide-gated ion channels.","authors":"Wassim Elkhatib, Adriano Senatore","doi":"10.1016/j.bpj.2025.02.027","DOIUrl":"10.1016/j.bpj.2025.02.027","url":null,"abstract":"","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":"143555798","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":"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":"<p><p>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.</p>","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}

{"title":"Morphological trapping of neurotransmitters in synaptic clefts: A new dimension in neural plasticity.","authors":"Bugra Kaytanli, Mattia Bacca","doi":"10.1016/j.bpj.2025.02.026","DOIUrl":"10.1016/j.bpj.2025.02.026","url":null,"abstract":"","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536384","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":"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":"<p><p>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 ∝ -n^k) 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.</p>","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}

{"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":"<p><p>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.</p>","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}