Biophysical journal最新文献

{"title":"Stomatocyte-discocyte-echinocyte transformations of erythrocyte modulated by membrane-cytoskeleton mechanical properties.","authors":"Haizhou Wen, Xuejin Li, Yu Lu, Xinyue Liu, Guohui Hu","doi":"10.1016/j.bpj.2024.12.001","DOIUrl":"10.1016/j.bpj.2024.12.001","url":null,"abstract":"<p><p>Stomatocyte-discocyte-echinocyte (SDE) transformations in human red blood cells (RBCs) have significant influences on blood dynamics and related disorders. The mechanical properties of the RBC membrane, such as shear modulus and bending elasticity, play crucial roles in determining RBC shapes. Recent biophysical findings reveal that building a comprehensive model capable of describing SDE shape transformations is a challenging problem. Based on dissipative particle dynamics, this study develops a two-component RBC model considering the detachment between the lipid bilayer and cytoskeleton, as well as the cytoskeletal reorganization during echinocyte formation. This model is validated by comparing RBCs' geometric shape and the apparent membrane tension with previous experimental measurements. Results indicate that a complete SDE sequence represented by six typical shapes can be obtained by modulating the model's mechanical and geometric parameters. Furthermore, a phase diagram based on reduced variables is obtained using principal-component analysis, demonstrating the phase transformations among SDE shapes. Our result suggests that the transformation from discocyte to stomatocyte is primarily influenced by dimensionless bending rigidity, whereas, during echinocyte formation, three key variables, i.e., dimensionless bending rigidity, targeting cytoskeleton shrinkage ratio, and connecting pattern, have joint impacts on the formation of spicules or bumps and the development of the cytoskeletal framework. The present two-component RBC model and the associated findings provide a perspective for a deeper understanding of the SDE transformation mechanism. This framework offers new insights into biological science and potential applications in the field of biomedical engineering.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791155","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":"Full identification of a growing and branching network's spatio-temporal structures.","authors":"Thibault Chassereau, Florence Chapeland-Leclerc, Éric Herbert","doi":"10.1016/j.bpj.2024.12.002","DOIUrl":"10.1016/j.bpj.2024.12.002","url":null,"abstract":"<p><p>Experimentally monitoring the kinematics of branching network growth is a tricky task, given the complexity of the structures generated in three dimensions. One option is to drive the network in such a way as to obtain two-dimensional growth, enabling a collection of independent images to be obtained. The density of the network generates ambiguous structures, such as overlaps and meetings, which hinder the reconstruction of the chronology of connections. In this paper, we propose a general method for global network reconstruction. Each network connection is defined by a unique label, enabling it to be tracked in time and space. In this work, we distinguish between lateral and apical branches on the one hand, and extremities on the other. Finally, we reconstruct the network after identifying and eliminating overlaps. This method is then applied to the model filamentous fungus Podospora anserina to reconstruct its growing thallus. We derive criteria for differentiating between apical and lateral branches. We find that the outer ring is favorably composed of apical branches, while densification within the network comes from lateral branches. From this, we derive the specific dynamics of each of the two types. Finally, in the absence of any latency phase during growth initiation, we can reconstruct a time based on the equality of apical and lateral branching collections. This makes it possible to directly compare the growth dynamics of different thalli.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791098","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":"Low-side and multi-tone suppression in the base of the gerbil cochlea.","authors":"C Elliott Strimbu, Elizabeth S Olson","doi":"10.1016/j.bpj.2024.12.004","DOIUrl":"https://doi.org/10.1016/j.bpj.2024.12.004","url":null,"abstract":"<p><p>The cochlea's mechanical response to sound stimulation is nonlinear, likely due to saturation of the mechano-electric transduction current that is part of an electromechanical feedback loop. The ability of a second tone or tones to reduce the response to a probe tone is one manifestation of nonlinearity, termed suppression. Using optical coherence tomography to measure motion within the organ of Corti, regional motion variations have been observed. Here, we report on the suppression that occurs within the organ of Corti when a high sound level, low frequency suppressor tone was delivered along with a sweep of discreet single-tones. Responses were measured in the base of the gerbil cochlea at two best frequency locations, with two different directions of observation relative to the sensory tissue's anatomical axes. Suppression extended over a wide frequency range in the outer hair cell region, whereas it was typically limited to the best frequency peak in the reticular lamina region and at the basilar membrane. Aspects of the observed suppression were consistent with the effect of a saturating nonlinearity. Recent measurements have noted the three-dimensional nature of organ of Corti motion. The effects of suppression observed here could be due to a combination of reduced motion amplitude and altered vibration axis.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784045","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":"Roles for PKC signaling in chromaffin cell exocytosis.","authors":"Xiaohuan Chen, Nicole A Bell, Breanna L Coffman, David R Giovannucci, Arun Anantharam","doi":"10.1016/j.bpj.2024.12.005","DOIUrl":"10.1016/j.bpj.2024.12.005","url":null,"abstract":"<p><p>Chromaffin cells of the adrenal medulla have an important role in the sympathetic stress response. They secrete catecholamines and other hormones into the bloodstream upon stimulation by the neurotransmitter pituitary adenylate cyclase-activating polypeptide (PACAP). PACAP causes a long-lasting and robust secretory response from chromaffin cells. However, the cellular mechanisms by which PACAP causes secretion remain unclear. Our previous work showed that the secretory response to PACAP relies on signaling through phospholipase C epsilon (PLCε). The objective of this study was to clarify the role of signaling events downstream of PLCε. Here, it is demonstrated that a brief exposure of chromaffin cells to PACAP caused diacylglycerol (DAG) production-a process that was dependent on PLCε activity. DAG then activated protein kinase C (PKC), prompting its redistribution to the plasma membrane. PKC activation was important for the increases in cytosolic Ca²⁺ and exocytosis that were evoked by PACAP. Indeed, pharmacological inhibition of PKC with NPC 15437, a competitive inhibitor of DAG binding, significantly disrupted the secretory response. NPC 15437 application also eliminated PACAP-stimulated effects on the readily releasable pool size, the Ca²⁺ sensitivity of granule fusion, and the voltage dependence of Ca²⁺ channel activation. Quantitative PCR revealed PKCβ, PKCε, and PKCμ to be highly expressed in the mouse chromaffin cell. Genetic knockdown of PKCβ and PKCε disrupted PACAP-evoked secretion, while knockdown of PKCμ had no measurable effect. This study highlights important roles for PKC signaling in a highly regulated pathway for exocytosis that is stimulated by PACAP.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784048","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":"Empirical methods that provide physical descriptions of dynamic cellular processes.","authors":"Ian Seim, Stephan W Grill","doi":"10.1016/j.bpj.2024.12.003","DOIUrl":"10.1016/j.bpj.2024.12.003","url":null,"abstract":"<p><p>We review empirical methods that can be used to provide physical descriptions of dynamic cellular processes during development and disease. Our focus will be nonspatial descriptions and the inference of underlying interaction networks including cell-state lineages, gene regulatory networks, and molecular interactions in living cells. Our overarching questions are: How much can we learn from just observing? To what degree is it possible to infer causal and/or precise mathematical relationships from observations? We restrict ourselves to data sets arising from only observations, or experiments in which minimal perturbations have taken place to facilitate observation of the systems as they naturally occur. We discuss analysis perspectives in order from those offering the least descriptive power but requiring the least assumptions such as statistical associations. We end with those that are most descriptive, but require stricter assumptions and more previous knowledge of the systems such as causal inference and dynamical systems approaches. We hope to provide and encourage the use of a wide array of options for quantitative cell biologists to learn as much as possible from their observations at all stages of understanding of their system of interest. Finally, we provide our own recipe of how to empirically determine quantitative relationships and growth laws from live-cell microscopy data, the resultant predictions of which can then be verified with perturbation experiments. We also include an extended supplement that describes further inference algorithms and theory for the interested reader.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784043","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":"Dynamic processes of fate decision in inducible bistable systems.","authors":"Sijing Chen, Yanhong Sun, Fengyu Zhang, Chunxiong Luo","doi":"10.1016/j.bpj.2024.10.015","DOIUrl":"10.1016/j.bpj.2024.10.015","url":null,"abstract":"<p><p>The process of biological fate decision regulated by gene regulatory networks involves numerous complex dynamical interactions among many components. Mathematical modeling typically employed ordinary differential equations and steady-state analysis, which has yielded valuable quantitative insights. However, stable states predicted by theoretical models often fail to capture transient or metastable phenomena that occur during most observation periods in experimental or real biological systems. We attribute this discrepancy to the omission of dynamic processes of various complex interactions. Here, we demonstrate the influence of delays in gene regulatory steps and the timescales of the external induction on the dynamic processes of the fate decision in inducible bistable systems. We propose that steady-state parameters determine the landscape of fate decision. However, during the dynamic evolution along the landscape, the unequal delays of biochemical interactions as well as the timescale of external induction cause deviations in the differentiation trajectories, leading to the formation of new transient distributions that persist long term. Our findings emphasize the importance of considering dynamic processes in fate decision instead of relying solely on steady-state analysis. We provide insights into the interpretation of experimental phenomena and offer valuable guidance for future efforts in dynamical modeling and synthetic biology design.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"4030-4041"},"PeriodicalIF":3.2,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628857/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543338","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":"Morphology and intervesicle distances in condensates of synaptic vesicles and synapsin.","authors":"Charlotte Neuhaus, Jette Alfken, Jakob Frost, Lauren Matthews, Christian Hoffmann, Marcelo Ganzella, Dragomir Milovanovic, Tim Salditt","doi":"10.1016/j.bpj.2024.11.004","DOIUrl":"10.1016/j.bpj.2024.11.004","url":null,"abstract":"<p><p>Synaptic vesicle clusters or pools are functionally important constituents of chemical synapses. In the so-called reserve and the active pools, neurotransmitter-loaded synaptic vesicles (SVs) are stored and conditioned for fusion with the synaptic membrane and subsequent neurotransmitter release during synaptic activity. Vesicle clusters can be considered as so-called membraneless compartments, which form by liquid-liquid phase separation. Synapsin as one of the most abundant synaptic proteins has been identified as a major driver of pool formation. It has been shown to induce liquid-liquid phase separation and form condensates on its own in solution, but also has been shown to integrate vesicles into condensates in vitro. In this process, the intrinsically disordered region of synapsin is believed to play a critical role. Here, we first investigate the solution structure of synapsin and SVs separately by small-angle x-ray scattering. In the limit of low momentum transfer q, the scattering curve for synapsin gives clear indication for supramolecular aggregation (condensation). We then study mixtures of SVs and synapsin-forming condensates, aiming at the morphology and intervesicle distances, i.e., the structure of the condensates in solution. To obtain the structure factor S(q) quantifying intervesicle correlation, we divide the scattering curve of condensates by that of pure SV suspensions. Analysis of S(q) in combination with numerical simulations of cluster aggregation indicates a noncompact fractal-like vesicular fluid with rather short intervesicle distances at the contact sites.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"4123-4134"},"PeriodicalIF":3.2,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613955","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":"Phonons reveal coupled cholesterol-lipid dynamics in ternary membranes.","authors":"James E Fitzgerald, Dmytro Soloviov, Yong Q Cai, Frederick A Heberle, Daisuke Ishikawa, Alfred Q R Baron, Dima Bolmatov, Mikhail Zhernenkov, Edward R Lyman","doi":"10.1016/j.bpj.2024.10.017","DOIUrl":"10.1016/j.bpj.2024.10.017","url":null,"abstract":"<p><p>Experimental studies of collective dynamics in lipid bilayers have been challenging due to the energy resolution required to observe these low-energy phonon-like modes. However, inelastic x-ray scattering (IXS) measurements-a technique for probing vibrations in soft and biological materials-are now possible with sub-meV resolution, permitting direct observation of low-energy, phonon-like modes in lipid membranes. Here, IXS measurements with sub-meV energy resolution reveal a low-energy optic-like phonon mode at roughly 3 meV in the liquid-ordered (L_o) and liquid-disordered phases of a ternary lipid mixture. This mode is only observed experimentally at momentum transfers greater than 5 nm^-1 in the L_o system. A similar gapped mode is also observed in all-atom molecular dynamics (MD) simulations of the same mixture, indicating that the simulations accurately represent the fast, collective dynamics in the L_o phase. Its optical nature and the Q range of the gap together suggest that the observed mode is due to the coupled motion of cholesterol-lipid pairs, separated by several hydrocarbon chains within the membrane plane. Analysis of the simulations provides molecular insight into the origin of the mode in transient, nanoscale substructures of hexagonally packed hydrocarbon chains. This nanoscale hexagonal packing was previously reported based on MD simulations and, later, by NMR measurements. Here, however, the integration of IXS and MD simulations identifies a new signature of the L_o substructure in the collective lipid dynamics, thanks to the recent confluence of IXS sensitivity and MD simulation capabilities.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"4042-4049"},"PeriodicalIF":3.2,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582069","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":"Multifocal lipid membrane characterization by combination of DAS-deconvolution and anisotropy.","authors":"Natsuumi Ito, Nozomi Morishita Watanabe, Yukihiro Okamoto, Hiroshi Umakoshi","doi":"10.1016/j.bpj.2024.11.005","DOIUrl":"10.1016/j.bpj.2024.11.005","url":null,"abstract":"<p><p>Three analog solvatochromic probes, Laurdan, Prodan, and Acdan, are extensively used in the study of biological sciences. Their locations in lipid membranes vary greatly in depth, and their fluorescence responds to their surrounding environment based on their corresponding locations in the membrane. Utilizing the fluorescence lifetimes (τ) and emission peak positions (λ) acquired from the time-resolved emission spectrum, one can effectively determine the local lipid environment using the analytical approach, referred to as τ and λ plots. Herein, a τ and λ plot was created using the aforementioned probes to expand the analytical field according to their location. Furthermore, the solvent modeling method in the τ and λ plot was upgraded to artificially emulate the complex environment in lipid membranes by utilizing liquid paraffin and glycerol to assess the contribution of viscosity to each fluorescence distribution. According to the results from a series of solvent mixtures, the effect of solvent viscosity on lifetime values was confirmed in the short lifetime region (τ < 3 ns). However, it was impossible to emulate the longer than 4 ns lifetime values observed in lipid membranes containing 1,2-dipalmitoyl-sn-glycero-3-phosphocholine in the range of viscosity applied in this study. From the insight of the limiting anisotropy (r_∞), the τ and λ plot was divided into a solvent-like region with an isotropic environment (r_∞ < 0.15) and a region highly ordered enough to define it as an anisotropic environment (0.15 < r_∞) at τ = 4 ns. Also, the membrane-specific distribution was illustrated as 4 ns < τ and λ < 460 nm from this work. An updated analytical model was created to visualize multiple fluorescence components of each probe in six types of lipid bilayers, confirming the different distributions between these probes. Our results well illustrate the multiplicity of lipid environments modeled with solvent and ordered environments in each lipid bilayer system.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"4135-4146"},"PeriodicalIF":3.2,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602817","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":"Conformations of a low-complexity protein in homogeneous and phase-separated frozen solutions.","authors":"C Blake Wilson, Myungwoon Lee, Wai-Ming Yau, Robert Tycko","doi":"10.1016/j.bpj.2024.11.001","DOIUrl":"10.1016/j.bpj.2024.11.001","url":null,"abstract":"<p><p>Solutions of the intrinsically disordered, low-complexity domain of the FUS protein (FUS-LC) undergo liquid-liquid phase separation (LLPS) below a temperature T_LLPS. To investigate whether local conformational distributions are detectably different in the homogeneous (i.e., single-phase) and phase-separated states of FUS-LC, we performed solid-state NMR (ssNMR) measurements on solutions that were frozen on submillisecond timescales after equilibration at temperatures well above (50°C) or well below (4°C) T_LLPS. Measurements were performed at 25 K with signal enhancements from dynamic nuclear polarization. Crosspeak patterns in two-dimensional ssNMR spectra of rapidly frozen solutions in which FUS-LC was uniformly ¹⁵N,¹³C labeled were found to be nearly identical for the two states. Similar results were obtained for solutions in which FUS-LC was labeled only at Thr, Tyr, and Gly residues, as well as solutions of a FUS construct in which five specific residues were labeled by ligation of synthetic and recombinant fragments. These experiments show that local conformational distributions are nearly the same in the homogeneous and phase-separated solutions, despite the much greater protein concentrations and more abundant intermolecular interactions within phase-separated, protein-rich \"droplets.\" Comparison of the experimental results with simulations of the sensitivity of two-dimensional ssNMR crosspeaks to changes in populations of β strand-like conformations suggests that changes in conformational distributions are no larger than 5-10%.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"4097-4114"},"PeriodicalIF":3.2,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575265","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}