Note: When clicking on a Digital Object Identifier (DOI) number, you will be taken to an external site maintained by the publisher.
Some full text articles may not yet be available without a charge during the embargo (administrative interval).
What is a DOI Number?
Some links on this page may take you to non-federal websites. Their policies may differ from this site.
-
Bulges in the plasma membrane of cells known as blebs can form spontaneously in a wide range of biological processes but what controls their shape and stability remains incompletely understood. To address this, we introduce a dual phase-field model with coupled order parameters representing the cell cortex and plasma membrane that can quantitatively model blebbing in three dimensions. Simulations and analysis of the model reveal that, depending on whether blebbing occurs by detachment of the plasma membrane or rupture of the actin cortex, blebs can form discontinuously through a saddle node bifurcation or continuously with increasing cortical tension. The model predictions are in good quantitative agreement with existing experimental data for laser-induced cortex rupture.more » « lessFree, publicly-accessible full text available March 17, 2026
-
Abstract We introduce a general phenomenological framework for understanding how phenotypic plasticity gives rise to drug persisters. These persisters, often quiescent but sometimes which again return to cycling, survive in the presence of treatment and eventually can lead to mutants with true resistance. Our framework builds on recent experimental observations regarding variations between and among single-cell clones and the possible role of the drug itself in enhancing the survival strategy. Predictions of our approach include the existence of an optimum drug concentration as well as an optimum drug holiday schedule to minimize the persistence-based threat.more » « lessFree, publicly-accessible full text available January 24, 2026
-
Free, publicly-accessible full text available February 1, 2026
-
Free, publicly-accessible full text available February 1, 2026
-
Adaptive immune systems engage in an arms race with evolving viruses, trying to generate new responses to viral strains that continually move away from the set of genetically varying strains that have already elicited a functional immune response. It has been argued that this dynamical process can lead to a propagating pulse of an ever-changing viral population and concomitant immune response. Here, we introduce a new stochastic model of viral-host coevolution, taking into account finite-sized host populations and varying processes of immune “forgetting”. Using both stochastic and deterministic calculations, we show that there is indeed a possible pulse solution, but for a large host population size and for finite memory capacity, the pulse becomes unstable to the generation of new infections in its wake. This instability leads to an extended endemic infection pattern, demonstrating that the population-level behavior of virus infections can exhibit a wider range of behavior than had been previously realized. Published by the American Physical Society2024more » « lessFree, publicly-accessible full text available September 1, 2025
-
This article introduces a special issue on the interaction between the rapidly expanding field of machine learning and ongoing research in physics. The first half of the papers in this issue deals with the question, what can machine learning do for physics? The second part asks the reverse, what can physics do for machine learning? As we will see, both of these directions are being vigorously pursued.more » « less
-
Transcription has a mechanical component, as the translocation of the transcription machinery or RNA polymerase (RNAP) on DNA or chromatin is dynamically coupled to the chromatin torsion. This posits chromatin mechanics as a possible regulator of eukaryotic transcription, however, the modes and mechanisms of this regulation are elusive. Here, we first take a statistical mechanics approach to model the torsional response of topology-constrained chromatin. Our model recapitulates the experimentally observed weaker torsional stiffness of chromatin compared to bare DNA and proposes structural transitions of nucleosomes into chirally distinct states as the driver of the contrasting torsional mechanics. Coupling chromatin mechanics with RNAP translocation in stochastic simulations, we reveal a complex interplay of DNA supercoiling and nucleosome dynamics in governing RNAP velocity. Nucleosomes play a dual role in controlling the transcription dynamics. The steric barrier aspect of nucleosomes in the gene body counteracts transcription via hindering RNAP motion, whereas the chiral transitions facilitate RNAP motion via driving a low restoring torque upon twisting the DNA. While nucleosomes with low dissociation rates are typically transcriptionally repressive, highly dynamic nucleosomes offer less of a steric barrier and enhance the transcription elongation dynamics of weakly transcribed genes via buffering DNA twist. We use the model to predict transcription-dependent levels of DNA supercoiling in segments of the budding yeast genome that are in accord with available experimental data. The model unveils a paradigm of DNA supercoiling-mediated interaction between genes and makes testable predictions that will guide experimental design.more » « less
-
Exploring the complexity of the epithelial-to-mesenchymal transition (EMT) unveils a diversity of potential cell fates; however, the exact timing and mechanisms by which early cell states diverge into distinct EMT trajectories remain unclear. Studying these EMT trajectories through single-cell RNA sequencing is challenging due to the necessity of sacrificing cells for each measurement. In this study, we employed optimal-transport analysis to reconstruct the past trajectories of different cell fates during TGF-beta-induced EMT in the MCF10A cell line. Our analysis revealed three distinct trajectories leading to low EMT, partial EMT, and high EMT states. Cells along the partial EMT trajectory showed substantial variations in the EMT signature and exhibited pronounced stemness. Throughout this EMT trajectory, we observed a consistent downregulation of theEEDandEZH2genes. This finding was validated by recent inhibitor screens of EMT regulators and CRISPR screen studies. Moreover, we applied our analysis of early-phase differential gene expression to gene sets associated with stemness and proliferation, pinpointingITGB4,LAMA3, andLAMB3as genes differentially expressed in the initial stages of the partial versus high EMT trajectories. We also found thatCENPF,CKS1B, andMKI67showed significant upregulation in the high EMT trajectory. While the first group of genes aligns with findings from previous studies, our work uniquely pinpoints the precise timing of these upregulations. Finally, the identification of the latter group of genes sheds light on potential cell cycle targets for modulating EMT trajectories.more » « lessFree, publicly-accessible full text available August 6, 2025
-
Reliable prediction of T cell specificity against antigenic signatures is a formidable task, complicated by the immense diversity of T cell receptor and antigen sequence space and the resulting limited availability of training sets for inferential models. Recent modeling efforts have demonstrated the advantage of incorporating structural information to overcome the need for extensive training sequence data, yet disentangling the heterogeneous TCR-antigen interface to accurately predict MHC-allele-restricted TCR-peptide interactions has remained challenging. Here, we present RACER-m, a coarse-grained structural model leveraging key biophysical information from the diversity of publicly available TCR-antigen crystal structures. Explicit inclusion of structural content substantially reduces the required number of training examples and maintains reliable predictions of TCR-recognition specificity and sensitivity across diverse biological contexts. Our model capably identifies biophysically meaningful point-mutant peptides that affect binding affinity, distinguishing its ability in predicting TCR specificity of point-mutants from alternative sequence-based methods. Its application is broadly applicable to studies involving both closely related and structurally diverse TCR-peptide pairs.more » « less