Physical biology最新文献_第2页

Mechanical compression regulates tumor spheroid invasion into a 3D collagen matrix 机械压缩调节肿瘤小球向三维胶原基质的侵袭

IF 2 4区生物学

Physical biology Pub Date : 2024-04-15 DOI: 10.1088/1478-3975/ad3ac5

Mrinal Pandey, Young Joon Suh, Minha Kim, Hannah Jane Davis, Jeffrey E Segall, Mingming Wu

{"title":"Mechanical compression regulates tumor spheroid invasion into a 3D collagen matrix","authors":"Mrinal Pandey, Young Joon Suh, Minha Kim, Hannah Jane Davis, Jeffrey E Segall, Mingming Wu","doi":"10.1088/1478-3975/ad3ac5","DOIUrl":"https://doi.org/10.1088/1478-3975/ad3ac5","url":null,"abstract":"Uncontrolled growth of tumor cells in confined spaces leads to the accumulation of compressive stress within the tumor. Although the effects of tension within 3D extracellular matrices (ECMs) on tumor growth and invasion are well established, the role of compression in tumor mechanics and invasion is largely unexplored. In this study, we modified a Transwell assay such that it provides constant compressive loads to spheroids embedded within a collagen matrix. We used microscopic imaging to follow the single cell dynamics of the cells within the spheroids, as well as invasion into the 3D ECMs. Our experimental results showed that malignant breast tumor (MDA-MB-231) and non-tumorigenic epithelial (MCF10A) spheroids responded differently to a constant compression. Cells within the malignant spheroids became more motile within the spheroids and invaded more into the ECM under compression; whereas cells within non-tumorigenic MCF10A spheroids became less motile within the spheroids and did not display apparent detachment from the spheroids under compression. These findings suggest that compression may play differential roles in healthy and pathogenic epithelial tissues and highlight the importance of tumor mechanics and invasion.","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140616327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dynamical model of antibiotic responses linking expression of resistance genes to metabolism explains emergence of heterogeneity during drug exposures. 抗生素反应动态模型将抗药性基因的表达与新陈代谢联系起来，解释了药物接触过程中出现的异质性。

IF 2 4区生物学

Physical biology Pub Date : 2024-04-02 DOI: 10.1088/1478-3975/ad2d64

Mirjana Stevanovic, João Pedro Teuber Carvalho, Philip Bittihn, Daniel Schultz

{"title":"Dynamical model of antibiotic responses linking expression of resistance genes to metabolism explains emergence of heterogeneity during drug exposures.","authors":"Mirjana Stevanovic, João Pedro Teuber Carvalho, Philip Bittihn, Daniel Schultz","doi":"10.1088/1478-3975/ad2d64","DOIUrl":"10.1088/1478-3975/ad2d64","url":null,"abstract":"Antibiotic responses in bacteria are highly dynamic and heterogeneous, with sudden exposure of bacterial colonies to high drug doses resulting in the coexistence of recovered and arrested cells. The dynamics of the response is determined by regulatory circuits controlling the expression of resistance genes, which are in turn modulated by the drug's action on cell growth and metabolism. Despite advances in understanding gene regulation at the molecular level, we still lack a framework to describe how feedback mechanisms resulting from the interdependence between expression of resistance and cell metabolism can amplify naturally occurring noise and create heterogeneity at the population level. To understand how this interplay affects cell survival upon exposure, we constructed a mathematical model of the dynamics of antibiotic responses that links metabolism and regulation of gene expression, based on the tetracycline resistancetetoperon inE. coli. We use this model to interpret measurements of growth and expression of resistance in microfluidic experiments, both in single cells and in biofilms. We also implemented a stochastic model of the drug response, to show that exposure to high drug levels results in large variations of recovery times and heterogeneity at the population level. We show that stochasticity is important to determine how nutrient quality affects cell survival during exposure to high drug concentrations. A quantitative description of how microbes respond to antibiotics in dynamical environments is crucial to understand population-level behaviors such as biofilms and pathogenesis.","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10988634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139983583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural maturation of myofilaments in engineered 3D cardiac microtissues characterized using small angle x-ray scattering. 利用小角 X 射线散射表征工程三维心脏微组织中肌丝的结构成熟。

IF 2 4区生物学

Physical biology Pub Date : 2024-03-20 DOI: 10.1088/1478-3975/ad310e

Geoffrey van Dover, Josh Javor, Jourdan K Ewoldt, Mikhail Zhernenkov, Patryk Wąsik, Guillaume Freychet, Josh Lee, Dana Brown, Christopher S Chen, David J Bishop

{"title":"Structural maturation of myofilaments in engineered 3D cardiac microtissues characterized using small angle x-ray scattering.","authors":"Geoffrey van Dover, Josh Javor, Jourdan K Ewoldt, Mikhail Zhernenkov, Patryk Wąsik, Guillaume Freychet, Josh Lee, Dana Brown, Christopher S Chen, David J Bishop","doi":"10.1088/1478-3975/ad310e","DOIUrl":"10.1088/1478-3975/ad310e","url":null,"abstract":"Understanding the structural and functional development of human-induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs) is essential to engineering cardiac tissue that enables pharmaceutical testing, modeling diseases, and designing therapies. Here we use a method not commonly applied to biological materials, small angle x-ray scattering, to characterize the structural development of hiPSC-CMs within three-dimensional engineered tissues during their preliminary stages of maturation. An x-ray scattering experimental method enables the reliable characterization of the cardiomyocyte myofilament spacing with maturation time. The myofilament lattice spacing monotonically decreases as the tissue matures from its initial post-seeding state over the span of 10 days. Visualization of the spacing at a grid of positions in the tissue provides an approach to characterizing the maturation and organization of cardiomyocyte myofilaments and has the potential to help elucidate mechanisms of pathophysiology, and disease progression, thereby stimulating new biological hypotheses in stem cell engineering.","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140060350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Coupled action potential and calcium dynamics underlie robust spontaneous firing in dopaminergic neurons. 动作电位和钙动力学耦合是多巴胺能神经元强劲自发点火的基础。

IF 2 4区生物学

Physical biology Pub Date : 2024-03-01 DOI: 10.1088/1478-3975/ad2bd4

Hadeel Khamis, Ohad Cohen

{"title":"Coupled action potential and calcium dynamics underlie robust spontaneous firing in dopaminergic neurons.","authors":"Hadeel Khamis, Ohad Cohen","doi":"10.1088/1478-3975/ad2bd4","DOIUrl":"10.1088/1478-3975/ad2bd4","url":null,"abstract":"Dopaminergic neurons are specialized cells in the substantia nigra, tasked with dopamine secretion. This secretion relies on intracellular calcium signaling coupled to neuronal electrical activity. These neurons are known to display spontaneous calcium oscillationsin-vitroandin-vivo, even in synaptic isolation, controlling the basal dopamine levels. Here we outline a kinetic model for the ion exchange across the neuronal plasma membrane. Crucially, we relax the assumption of constant, cytoplasmic sodium and potassium concentration. We show that sodium-potassium dynamics are strongly coupled to calcium dynamics and are essential for the robustness of spontaneous firing frequency. The model predicts several regimes of electrical activity, including tonic and 'burst' oscillations, and predicts the switch between those in response to perturbations. 'Bursting' correlates with increased calcium amplitudes, while maintaining constant average, allowing for a vast change in the calcium signal responsible for dopamine secretion. All the above traits provide the flexibility to create rich action potential dynamics that are crucial for cellular function.","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139932493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Modeling cancer progression: an integrated workflow extending data-driven kinetic models to bio-mechanical PDE models. 癌症进展建模：将数据驱动的动力学模型扩展到生物力学 PDE 模型的综合工作流程。

IF 2 4区生物学

Physical biology Pub Date : 2024-02-19 DOI: 10.1088/1478-3975/ad2777

Navid Mohammad Mirzaei, Leili Shahriyari

引用次数: 0

An effective hydrodynamic description of marching locusts. 蝗虫行进的有效流体力学描述。

IF 2 4区生物学

Physical biology Pub Date : 2024-02-14 DOI: 10.1088/1478-3975/ad2219

Dan Gorbonos, Felix B Oberhauser, Luke L Costello, Yannick Günzel, Einat Couzin-Fuchs, Benjamin Koger, Iain D Couzin

{"title":"An effective hydrodynamic description of marching locusts.","authors":"Dan Gorbonos, Felix B Oberhauser, Luke L Costello, Yannick Günzel, Einat Couzin-Fuchs, Benjamin Koger, Iain D Couzin","doi":"10.1088/1478-3975/ad2219","DOIUrl":"10.1088/1478-3975/ad2219","url":null,"abstract":"A fundamental question in complex systems is how to relate interactions between individual components ('microscopic description') to the global properties of the system ('macroscopic description'). Furthermore, it is unclear whether such a macroscopic description exists and if such a description can capture large-scale properties. Here, we address the validity of a macroscopic description of a complex biological system using the collective motion of desert locusts as a canonical example. One of the world's most devastating insect plagues begins when flightless juvenile locusts form 'marching bands'. These bands display remarkable coordinated motion, moving through semiarid habitats in search of food. We investigated how well macroscopic physical models can describe the flow of locusts within a band. For this, we filmed locusts within marching bands during an outbreak in Kenya and automatically tracked all individuals passing through the camera frame. We first analyzed the spatial topology of nearest neighbors and found individuals to be isotropically distributed. Despite this apparent randomness, a local order was observed in regions of high density in the radial distribution function, akin to an ordered fluid. Furthermore, reconstructing individual locust trajectories revealed a highly aligned movement, consistent with the one-dimensional version of the Toner-Tu equations, a generalization of the Navier-Stokes equations for fluids, used to describe the equivalent macroscopic fluid properties of active particles. Using this effective Toner-Tu equation, which relates the gradient of the pressure to the acceleration, we show that the effective 'pressure' of locusts increases as a linear function of density in segments with the highest polarization (for which the one-dimensional approximation is most appropriate). Our study thus demonstrates an effective hydrodynamic description of flow dynamics in plague locust swarms.","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139545929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An individual-based model to explore the impact of psychological stress on immune infiltration into tumour spheroids. 基于个体的模型，探索心理压力对肿瘤球体内免疫渗透的影响。

IF 2 4区生物学

Physical biology Pub Date : 2024-02-05 DOI: 10.1088/1478-3975/ad221a

Emma Leschiera, Gheed Al-Hity, Melanie S Flint, Chandrasekhar Venkataraman, Tommaso Lorenzi, Luis Almeida, Chloe Audebert

{"title":"An individual-based model to explore the impact of psychological stress on immune infiltration into tumour spheroids.","authors":"Emma Leschiera, Gheed Al-Hity, Melanie S Flint, Chandrasekhar Venkataraman, Tommaso Lorenzi, Luis Almeida, Chloe Audebert","doi":"10.1088/1478-3975/ad221a","DOIUrl":"10.1088/1478-3975/ad221a","url":null,"abstract":"In recentin vitroexperiments on co-culture between breast tumour spheroids and activated immune cells, it was observed that the introduction of the stress hormone cortisol resulted in a decreased immune cell infiltration into the spheroids. Moreover, the presence of cortisol deregulated the normal levels of the pro- and anti-inflammatory cytokines IFN-γand IL-10. We present an individual-based model to explore the interaction dynamics between tumour and immune cells under psychological stress conditions. With our model, we explore the processes underlying the emergence of different levels of immune infiltration, with particular focus on the biological mechanisms regulated by IFN-γand IL-10. The set-up of numerical simulations is defined to mimic the scenarios considered in the experimental study. Similarly to the experimental quantitative analysis, we compute a score that quantifies the level of immune cell infiltration into the tumour. The results of numerical simulations indicate that the motility of immune cells, their capability to infiltrate through tumour cells, their growth rate and the interplay between these cell parameters can affect the level of immune cell infiltration in different ways. Ultimately, numerical simulations of this model support a deeper understanding of the impact of biological stress-induced mechanisms on immune infiltration.","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139546034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structure of the space of folding protein sequences defined by large language models. 由大型语言模型定义的折叠蛋白质序列空间结构。

IF 2 4区生物学

Physical biology Pub Date : 2024-01-31 DOI: 10.1088/1478-3975/ad205c

A Zambon, R Zecchina, G Tiana

{"title":"Structure of the space of folding protein sequences defined by large language models.","authors":"A Zambon, R Zecchina, G Tiana","doi":"10.1088/1478-3975/ad205c","DOIUrl":"10.1088/1478-3975/ad205c","url":null,"abstract":"Proteins populate a manifold in the high-dimensional sequence space whose geometrical structure guides their natural evolution. Leveraging recently-developed structure prediction tools based on transformer models, we first examine the protein sequence landscape as defined by an effective energy that is a proxy of sequence foldability. This landscape shares characteristics with optimization challenges encountered in machine learning and constraint satisfaction problems. Our analysis reveals that natural proteins predominantly reside in wide, flat minima within this energy landscape. To investigate further, we employ statistical mechanics algorithms specifically designed to explore regions with high local entropy in relatively flat landscapes. Our findings indicate that these specialized algorithms can identify valleys with higher entropy compared to those found using traditional methods such as Monte Carlo Markov Chains. In a proof-of-concept case, we find that these highly entropic minima exhibit significant similarities to natural sequences, especially in critical key sites and local entropy. Additionally, evaluations through Molecular Dynamics suggests that the stability of these sequences closely resembles that of natural proteins. Our tool combines advancements in machine learning and statistical physics, providing new insights into the exploration of sequence landscapes where wide, flat minima coexist alongside a majority of narrower minima.","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139491534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Fitness effects of a demography-dispersal trade-off in expandingSaccharomyces cerevisiaemats. 在不断扩大的酿酒酵母垫中，种群数量-散布权衡对体能的影响。

IF 2 4区生物学

Physical biology Pub Date : 2024-01-22 DOI: 10.1088/1478-3975/ad1ccd

Rebekah Hall, Akila Bandara, Daniel A Charlebois

{"title":"Fitness effects of a demography-dispersal trade-off in expandingSaccharomyces cerevisiaemats.","authors":"Rebekah Hall, Akila Bandara, Daniel A Charlebois","doi":"10.1088/1478-3975/ad1ccd","DOIUrl":"10.1088/1478-3975/ad1ccd","url":null,"abstract":"Fungi expand in space and time to form complex multicellular communities. The mechanisms by which they do so can vary dramatically and determine the life-history and dispersal traits of expanding populations. These traits influence deterministic and stochastic components of evolution, resulting in complex eco-evolutionary dynamics during colony expansion. We perform experiments on budding yeast strains genetically engineered to display rough-surface and smooth-surface phenotypes in colony-like structures called 'mats'. Previously, it was shown that the rough-surface strain has a competitive advantage over the smooth-surface strain when grown on semi-solid media. We experimentally observe the emergence and expansion of segments with a distinct smooth-surface phenotype during rough-surface mat development. We propose a trade-off between dispersal and local carrying capacity to explain the relative fitness of these two phenotypes. Using a modified stepping-stone model, we demonstrate that this trade-off gives the high-dispersing, rough-surface phenotype a competitive advantage from standing variation, but that it inhibits this phenotype's ability to invade a resident smooth-surface population via mutation. However, the trade-off improves the ability of the smooth-surface phenotype to invade in rough-surface mats, replicating the frequent emergence of smooth-surface segments in experiments. Together, these computational and experimental findings advance our understanding of the complex eco-evolutionary dynamics of fungal mat expansion.","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139404099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A thermodynamical model of non-deterministic computation in cortical neural networks 皮层神经网络非确定性计算的热力学模型

IF 2 4区生物学

Physical biology Pub Date : 2023-12-11 DOI: 10.1088/1478-3975/ad0f2d

Elizabeth A Stoll

{"title":"A thermodynamical model of non-deterministic computation in cortical neural networks","authors":"Elizabeth A Stoll","doi":"10.1088/1478-3975/ad0f2d","DOIUrl":"https://doi.org/10.1088/1478-3975/ad0f2d","url":null,"abstract":"Neuronal populations in the cerebral cortex engage in probabilistic coding, effectively encoding the state of the surrounding environment with high accuracy and extraordinary energy efficiency. A new approach models the inherently probabilistic nature of cortical neuron signaling outcomes as a thermodynamic process of non-deterministic computation. A mean field approach is used, with the trial Hamiltonian maximizing available free energy and minimizing the net quantity of entropy, compared with a reference Hamiltonian. Thermodynamic quantities are always conserved during the computation; free energy must be expended to produce information, and free energy is released during information compression, as correlations are identified between the encoding system and its surrounding environment. Due to the relationship between the Gibbs free energy equation and the Nernst equation, any increase in free energy is paired with a local decrease in membrane potential. As a result, this process of thermodynamic computation adjusts the likelihood of each neuron firing an action potential. This model shows that non-deterministic signaling outcomes can be achieved by noisy cortical neurons, through an energy-efficient computational process that involves optimally redistributing a Hamiltonian over some time evolution. Calculations demonstrate that the energy efficiency of the human brain is consistent with this model of non-deterministic computation, with net entropy production far too low to retain the assumptions of a classical system.","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2023-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138692326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0