PRX life最新文献

{"title":"Dissecting Rate-Limiting Processes in Biomolecular Condensate Exchange Dynamics.","authors":"Ross Kliegman, Eli Kengmana, Rebecca Schulman, Yaojun Zhang","doi":"10.1103/h9cl-j5x5","DOIUrl":"10.1103/h9cl-j5x5","url":null,"abstract":"<p><p>An increasing number of biomolecules have been shown to phase-separate into biomolecular condensates-membraneless subcellular compartments capable of regulating distinct biochemical processes within living cells. The speed with which they exchange components with the cellular environment can influence how fast biochemical reactions occur inside condensates and how fast condensates respond to environmental changes, thereby directly impacting condensate function. While fluorescence recovery after photobleaching (FRAP) experiments are routinely performed to measure this exchange timescale, it remains a challenge to distinguish the various physical processes limiting fluorescence recovery and identify each associated timescale. Here, we present a reaction-diffusion model for condensate exchange dynamics and show that such exchange can differ significantly from that of conventional liquid droplets due to the presence of a percolated molecular network, which gives rise to different mobility species in the dense phase. In this model, exchange can be limited by diffusion of either the high- or low-mobility species in the dense phase, diffusion in the dilute phase, or the attachment (detachment) of molecules to (from) the network at the surface or throughout the bulk of the condensate. Combining analytic derivations and numerical simulations, we quantify the contributions of these distinct physical processes to the overall exchange timescale and predict an experimentally testable scaling relationship between the exchange timescale and condensate size. Our theory suggests that the exchange dynamics can be accelerated via a pore-mediated pathway in which molecules pass through the pores of the meshwork and attach directly in the condensate interior. Notably, this pathway permits a parameter regime in which the exchange timescale becomes independent of condensate size, a scaling behavior that is supported by our FRAP measurements on a biosynthetic DNA nanostar system. Our work offers insight into the rate-limiting physical processes that can control condensate material exchange, with implications for natural and engineered systems.</p>","PeriodicalId":520261,"journal":{"name":"PRX life","volume":"4 3","pages":"033006"},"PeriodicalIF":0.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13645380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149140162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inheritance entropy: A model-independent method to probe the hereditary structure of cell lineage trees.","authors":"Alessandro Allegrezza, Riccardo Beschi, Domenico Caudo, Andrea Cavagna, Alessandro Corsi, Antonio Culla, Samantha Donsante, Giuseppe Giannicola, Irene Giardina, Giorgio Gosti, Tomás S Grigera, Stefania Melillo, Biagio Palmisano, Leonardo Parisi, Lorena Postiglione, Mara Riminucci, Francesco Saverio Rotondi","doi":"10.1103/p2mj-q682","DOIUrl":"10.1103/p2mj-q682","url":null,"abstract":"<p><p>Quantifying the impact of hereditary transmission within lineage trees remains a fundamental challenge universal to a wide array of biological domains. Here, we introduce the new concept of inheritance entropy, a quantity designed to gauge the hereditary structure of inactive cells across a lineage. We measure this entropy in 32 human stem cell clonal colonies, obtained from high-definition single-cell lineage tracing experiments, and show that in the greatest majority of clones the entropy is decisively smaller than that of the corresponding nonhereditary ensemble, hence proving that variations in the proliferative power of stem cell lineages are determined by hereditary epigenetic factors that regulate cell-cycle exit. The method can also be employed to locate the specific node of the tree where a mutation in the probability of inactivity occurs, together with a determination of the lag between the mutation ultimately leading to inactivity and its actual expression. This framework can be used to assess in a robust, simple and model-agnostic way the hereditary origin of differential growth in any type of lineage trees.</p>","PeriodicalId":520261,"journal":{"name":"PRX life","volume":"4 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7619470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148914965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Probabilistic Models, Compressible Interactions, and Neural Coding.","authors":"Luisa Ramirez, William Bialek, Stephanie E Palmer, David J Schwab","doi":"10.1103/pj4s-g4jc","DOIUrl":"10.1103/pj4s-g4jc","url":null,"abstract":"<p><p>In physics we often use very simple models to describe systems with many degrees of freedom, but it is not clear why or how this success can be transferred to the more complex biological context. We consider models for the joint distribution of many variables, as with the combinations of spiking and silence in large networks of neurons. In this probabilistic framework, we argue that simple models are possible if the mutual information between two halves of the system is consistently subextensive, and if this shared information is compressible. These conditions are not met generically, but they are met by real-world data, such as natural images and the activity in a population of retinal output neurons. We introduce compression strategies that combine the information bottleneck with an iteration scheme inspired by the renormalization group, and we find that the number of parameters needed to describe the distribution of joint activity scales with the square of the number of neurons, even though the interactions are not well approximated as pairwise. Our results also show that this shared information is essentially equal to the information that individual neurons carry about natural visual inputs, which has surprising implications for the neural code.</p>","PeriodicalId":520261,"journal":{"name":"PRX life","volume":"4 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13441408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148682083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lattice Ultrasensitivity Amplifies Signals in <i>E. coli</i> without Finely-Tuned Allosteric Interactions.","authors":"Derek M Sherry, Isabella R Graf, Samuel J Bryant, Thierry Emonet, Benjamin B Machta","doi":"10.1103/7dgz-l5fd","DOIUrl":"10.1103/7dgz-l5fd","url":null,"abstract":"<p><p>The <i>E. coli</i> chemosensory lattice, consisting of receptors, kinases, and adaptor proteins, is an important test case for biochemical signal processing. Kinase output is characterized by precise adaptation to a wide range of background ligand levels and large gain in response to small relative changes in concentration. Existing models of this lattice achieve their gain through allosteric interactions between either receptors or core units of receptors and kinases. Here we introduce a model which operates through an entirely different mechanism in which receptors gate inherently far from equilibrium enzymatic reactions between neighboring kinases. Our lattice model achieves gain through a mechanism more closely related to zero-order ultrasensitivity than to allostery. Thus, we call it lattice ultrasensitivity (LU). Unlike other lattice models with critical points, the LU model can achieve arbitrarily high gain through timescale separation, rather than through finely tuned allosteric interactions. The model also captures qualitative experimental results which are difficult to reconcile with existing models. We discuss possible implementations in the lattice's baseplate where long flexible linkers could potentially mediate interactions between neighboring core units.</p>","PeriodicalId":520261,"journal":{"name":"PRX life","volume":"4 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13449865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148698662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Membrane-Anchored Mobile Tethers Modulate Condensate Wetting, Localization, and Migration.","authors":"Qiwei Yu, Trevor GrandPre, Andrew G T Pyo, Andrej Košmrlj, Ned S Wingreen","doi":"10.1103/kxpb-9srd","DOIUrl":"10.1103/kxpb-9srd","url":null,"abstract":"<p><p>Biomolecular condensates frequently rely on membrane interactions for recruitment, localization, and biochemical substrates. Many of these interactions are mediated by membrane-anchored molecules such as proteins or specific lipids, which we refer to as \"mobile tethers\" since they can typically diffuse within the membrane while still interacting with the condensate. The presence of mobile tethers creates a surface with dynamic and spatially inhomogeneous wetting properties that are typically overlooked by traditional wetting theories. Here, we propose a general theoretical framework to study how mobile tethers impact both equilibrium and dynamic properties of condensate wetting. We show that a favorable tether-condensate interaction leads to tether enrichment at the condensate-membrane interface, which modifies the equilibrium condensate-membrane surface tension and contact angle. Increasing tether abundance on the membrane can drive transitions between wetting regimes, with only a modest tether density and binding energy required for biologically relevant scenarios. Furthermore, tethers modulate how condensates react to complex membrane geometries. By helping condensates coat membranes, mobile tethers can facilitate condensate localization to junctions of membrane structures, such as the reticulated membranes inside the algal pyrenoid. Both tether abundance and mobility affect how droplets interact with complex membrane geometries, such as droplet migration along membrane tubules of varying radii. These results provide a framework to study the implications of tether-mediated condensate-membrane interactions for cellular organization and function.</p>","PeriodicalId":520261,"journal":{"name":"PRX life","volume":"4 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13256346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148255325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How the Immune System Learns.","authors":"Arup K Chakraborty, Anupama Jayaraman, Daniel P Newton","doi":"10.1103/znt6-6n38","DOIUrl":"10.1103/znt6-6n38","url":null,"abstract":"<p><p>The adaptive immune system can mount pathogen-specific responses against a vast world of evolving pathogens (antigens). The humoral immune system is a part of adaptive immunity. It has the remarkable ability to learn about an antigen after exposure to it through a mutation-selection evolutionary process, resulting in more potent responses than those that emerge initially. Recent studies have revealed that upon reexposure to antigens, feedback regulation mediated by past responses steers the evolutionary learning algorithm to generate new responses. This feature enables the immune system to learn to generalize responses to target unseen variants of the original pathogen upon \"training\" with a limited number of samples. We summarize these new findings and suggest new questions that emerge from them. This is the right time to address these questions by bringing together statistical physics, machine learning, immunology, and evolutionary biology.</p>","PeriodicalId":520261,"journal":{"name":"PRX life","volume":"4 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13251631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148230475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell rearrangement progression along the apical-basal axis is linked with 3D epithelial tissue structure.","authors":"Erika M Kusaka, Sassan Ostvar, Xiaoyun Liu, Xun Wang, Tianyi Liu, Karen E Kasza","doi":"10.1103/l5r5-pb9t","DOIUrl":"10.1103/l5r5-pb9t","url":null,"abstract":"<p><p>Epithelial tissues undergo extensive structural remodeling during embryonic development. Tissue remodeling is often enabled by oriented cell rearrangements that are linked with patterns of mechanical stresses in the tissue and with tissue mechanical properties. Cell rearrangements and their links to tissue structure have largely been studied at the apical side of tissues at the level of adherens junctions. Less is known about the involvement of basolateral domains in cell rearrangements. Here we use live confocal imaging to quantify cell rearrangements, cell packing structure, and cell morphology in 3D in the converging and extending <i>Drosophila</i> germband epithelium. We report gradients in cell shapes and tissue structure along the apical-basal axis of the germband, suggesting that the apical and basolateral domains display distinct behaviors. Cell rearrangements initiate at apical as well as basolateral positions, with initiation frequencies also displaying a gradient along the apical-basal axis. Analyses of cell contact angles and non-muscle myosin II localization patterns during cell rearrangements indicate that rearrangements can be actively driven in lateral as well as in apical regions of the tissue. Following initiation, rearrangements propagate across the apical-basal axis and lateral cell contacts remodel; these events involve scutoids and other complex 3D cell shapes as intermediate states. These findings uncover novel aspects of the cell rearrangements that drive dynamic remodeling of epithelia and reveal links between rearrangements and gradients in tissue structure along the apical-basal axis.</p>","PeriodicalId":520261,"journal":{"name":"PRX life","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13166131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147937136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inherent Leakage of Hydrophobic Gating in BK Channels.","authors":"Zhiguang Jia, Jianhan Chen","doi":"10.1103/m89c-6vv7","DOIUrl":"10.1103/m89c-6vv7","url":null,"abstract":"<p><p>The big potassium (BK) channels remain open with a small limiting probability of <i>P</i> _o ~ 10^-7 at minimal Ca²⁺ and negative voltages < -100 mV. The molecular origin of such \"intrinsic opening\" are not understood. Here, free energy analysis of K+ permeation shows that intrinsic opening of BK channels is likely an inherent property of the vapor barrier, generated by hydrophobic dewetting of the inner pore in the Ca²⁺-free state. The vapor barrier only gives rise to a finite free energy barrier, of ~ 8 kcal/mol, and cannot completely shut down K⁺ flow even when the voltage sensor domains are fully deactivated. The resulting \"leaking\" currents can be measured at negative voltages as intrinsic opening. The shallow limiting slope of <i>P</i> _o at negative voltages arises primarily from the electric field effects on the permeating ion through the vapor barrier. We further demonstrate that the vapor barrier can be perturbed by truncation of the cytosolic domains, inner pore mutations, and ligand binding to the pore, leading to predicable changes in limiting slope measurements highly consistent with existing experimental data. Therefore, the intrinsic opening opens up an opportunity for direct experimental study of hydrophobic gating in BK and many other ion channels.</p>","PeriodicalId":520261,"journal":{"name":"PRX life","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13048780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147625332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Morphogen Patterning in Dynamic Tissues.","authors":"Alex M Plum, Mattia Serra","doi":"10.1103/h74q-3dgj","DOIUrl":"10.1103/h74q-3dgj","url":null,"abstract":"<p><p>Embryogenesis integrates morphogenesis-coordinated cell movements-with morphogen patterning and cell differentiation. While largely studied independently, morphogenesis and patterning often unfold simultaneously in early embryos. Yet, how cell movements affect morphogen transport and cells' exposure over time remains unclear, as most pattern formation models assume static tissues. Here, we develop a theoretical framework for morphogen patterning in dynamic tissues, recasting advection-reaction-diffusion equations in the cells' moving reference frames. This framework (i) elucidates how morphogenesis mediates morphogen transport and compartmentalization: cell-cell diffusive transport is enhanced at multicellular flow attractors, while repellers act as barriers, affecting cell fate induction and bifurcations. (ii) It formalizes cell-cell signaling ranges in dynamic tissues, deconfounding morphogenetic movements to identify which cells could communicate via morphogens. (iii) It provides two new nondimensional numbers to assess when and where morphogenesis affects morphogen transport. We demonstrate this framework by analyzing classical patterning models with common morphogenetic motifs as well as experimental tissue flows. Our work rationalizes dynamic tissue patterning in development, constraining candidate patterning mechanisms and parameters using accessible cell motion data.</p>","PeriodicalId":520261,"journal":{"name":"PRX life","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13045748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147625319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Energy injection in an epithelial cell monolayer indicated by negative viscosity.","authors":"Molly McCord, Jacob Notbohm","doi":"10.1103/9lnm-gm3j","DOIUrl":"10.1103/9lnm-gm3j","url":null,"abstract":"<p><p>Epithelial tissues are driven out of thermodynamic equilibrium by internally generated forces, causing complex patterns of motion. Even when both the forces and motion are measurable, it is not yet possible to relate the two, because the sources of energy injection and dissipation are often unclear. Here, we study how energy is transferred by developing a method to measure the effective viscosity from the shear stresses and strain rates within an epithelial cell monolayer. Interestingly, there emerged multicellular regions in which the relationship between shear stress and shear strain rate was negatively proportional, indicating a negative effective viscosity. The negative effective viscosity occurred in regions wherein cell stresses were less efficient at producing tissue deformations compared to regions of positive effective viscosity. Regions of negative effective viscosity consistently exhibited greater cell speed and vorticity, and the cells had elevated metabolic activity, reflecting an increased energy demand in these cells. Our study shows that negative effective viscosity is a useful means of quantifying the flow of energy in living matter.</p>","PeriodicalId":520261,"journal":{"name":"PRX life","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12724540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145829809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}