Estimating parameters of a stochastic cell invasion model with fluorescent cell cycle labelling using approximate Bayesian computation

We develop a parameter estimation method based on approximate Bayesian computation (ABC) for a stochastic cell invasion model using fluorescent cell cycle labelling with proliferation, migration and crowding effects. Previously, inference has been performed on a deterministic version of the model fitted to cell density data, and not all parameters were identifiable. Considering the stochastic model allows us to harness more features of experimental data, including cell trajectories and cell count data, which we show overcomes the parameter identifiability problem. We demonstrate that, while difficult to collect, cell trajectory data can provide more information about the parameters of the cell invasion model. To handle the intractability of the likelihood function of the stochastic model, we use an efficient ABC algorithm based on sequential Monte Carlo. Rcpp and MATLAB implementations of the simulation model and ABC algorithm used in this study are available at https://github.com/michaelcarr-stats/FUCCI.     

Fibroblasts Cultured on Nanowires Exhibit Low Motility,Impaired Cell Division,and DNA Damage

Nanowires are commonly used as tools for interfacing living cells, acting as biomolecule‐delivery vectors or electrodes. It is generally assumed that the small size of the nanowires ensures a minimal cellular perturbation, yet the effects of nanowires on cell migration and proliferation remain largely unknown. Fibroblast behaviour on vertical nanowire arrays is investigated, and it is shown that cell motility and proliferation rate are reduced on nanowires. Fibroblasts cultured on long nanowires exhibit failed cell division, DNA damage, increased ROS content and respiration. Using focused ion beam milling and scanning electron microscopy, highly curved but intact nuclear membranes are observed, showing no direct contact between the nanowires and the DNA. The nanowires possibly induce cellular stress and high respiration rates, which trigger the formation of ROS, which in turn results in DNA damage. These results are important guidelines to the design and interpretation of experiments involving nanowire‐based transfection and electrical characterization of living cells.     

Manipulation of cell membrane using carbon nanotube scaffold as a photoresponsive stimuli generator

We describe, for the first time, the perforation of the cell membrane in the targeted single cell based on the nanosecond pulsed near-infrared (NIR) laser irradiation of a thin film of carbon nanotubes that act as an effective photon absorber as well as stimuli generator. When the power of NIR laser is over 17.5 μJ/pulse, the cell membrane after irradiation is irreversibly disrupted and results in cell death. In sharp contrast, the perforation of the cell membrane occurs at suitable laser power (～15 μJ/pulse) without involving cell termination.     

Nanomaterials can dynamically steer cell responses to biological ligands

Traditional tissue regeneration approaches to activate cell behaviors on biomaterials rely on the use of extracellular-matrix-based or soluble growth-factor cues. In this article, a novel approach is highlighted to dynamically steer cellular phenomena such as cell motility based on nanoscale substratum features of biological ligands. Albumin-derived nanocarriers (ANCs) with variable nanoscale-size features are functionalized with fibronectin III9-10 matrix ligands, and their effects on primary human keratinocyte activation are investigated. The presentation of fibronectin fragments from ANCs significantly enhances cell migration as compared to free ligands at equivalent concentrations. Notably, cell migration is influenced by the size of the underlying ANCs even for variably sized ANCs covered in comparable levels of fibronectin fragment. For equivalent ligand concentrations, cell migration on the smaller-sized ANCs (30 and 50 nm) is significantly enhanced as compared to that on larger-sized ANCs (75 and 100 nm). In contrast, the enhancement of cell migration on nanocarriers is abolished by the use of immobilized, biofunctionalized ANCs, indicating that "dynamic" nanocarrier internalization events underlie the role of nanocarrier geometry on the differential regulation of cell migration kinetics. Uptake studies using fluorescent ANCs indicate that larger-sized ANCs cause delayed endocytic kinetics and hence could present barriers for internalization during the cell adhesion and motility processes. Motile cells exhibit diminished migration upon exposure to clathrin inhibitors, but not caveolin inhibitors, suggesting the role of clathrin-mediated endocytosis in facilitating cell migratory responsiveness to the nanocarriers. Overall, a monotonic relationship is found between the nanocarrier cytointernalization rate and the cell migration rate, suggesting the possibility of designing biointerfacial features for the dynamic control of cell migration. Thus, the functionalization of a mobile nanocarrier by a biorelevant ligand can be used to sensitize cellular motility activation to the adhesion ligands, and such nanocarrier interfaces can dynamically attune cell migration kinetics by modulating the uptake of the ligand-nanocarrier complex via nanocarrier size.     

Minimizing the risk of cancer: tissue architecture and cellular replication limits

Normal somatic cells are capable of only a limited number of divisions, which prevents unlimited cell proliferation and the onset of tumours. Cancer cells find ways to circumvent this obstacle, typically by expressing the enzyme telomerase and less often by alternative recombination strategies. Given this fundamental link between cellular replication limits and cancer, it is important to understand how a tissue''s architecture affects the replicative capacity of a cell population. We define this as the average number of remaining divisions at equilibrium. The lower the replication capacity, the lower the chances to escape the replication limit during abnormal growth when a tumour develops. In this paper, we examine how the replication capacity is influenced by defining characteristics of cell lineages, such as the number of intermediate cell compartments, self-renewal capability of cells and division rates. We describe an optimal tissue architecture that minimizes the replication capacity of dividing cells and thus the risk of cancer. Interestingly, some of the features that define an optimal tissue architecture have been documented in a variety of tissues, suggesting that they may have evolved as a cancer-protecting strategy in multicellular organisms.     

A Highly Efficient Tumor‐Targeting Nanoprobe with a Novel Cell Membrane Permeability Mechanism

Efficient tumor targeting has been a great challenge in the clinic for a very long time. The traditional targeting methods based on enhanced permeability and retention (EPR) effects show only an ≈5% targeting rate. To solve this problem, a new graphene‐based tumor cell nuclear targeting fluorescent nanoprobe (GTTN), with a new tumor‐targeting mechanism, is developed. GTTN is a graphene‐like single‐crystalline structure amphiphilic fluorescent probe with a periphery that is functionalized by sulfonic and hydroxyl groups. This probe has the characteristic of specific tumor cell targeting, as it can directly cross the cell membrane and specifically target to the tumor cell nucleus by the changed permeability of the tumor cell membranes in the tumor tissue. This new targeting mechanism is named the cell membrane permeability targeting (CMPT) mechanism, which is very different from the EPR effect. These probes can recognize tumor tissue at a very early stage and track the invasion and metastasis of tumor cells at the single cell level. The tumor‐targeting rate is improved from less than 5% to more than 50%. This achievement in efficient and accurate tumor cell targeting will speed up the arrival of a new era of tumor diagnosis and treatment.     

Robustness of differentiation cascades with symmetric stem cell division

Stem cells (SCs) perform the task of maintaining tissue homeostasis by both self-renewal and differentiation. While it has been argued that SCs divide asymmetrically, there is also evidence that SCs undergo symmetric division. Symmetric SC division has been speculated to be key for expanding cell numbers in development and regeneration after injury. However, it might lead to uncontrolled growth and malignancies such as cancer. In order to explore the role of symmetric SC division, we propose a mathematical model of the effect of symmetric SC division on the robustness of a population regulated by a serial differentiation cascade and we show that this may lead to extinction of such population. We examine how the extinction likelihood depends on defining characteristics of the population such as the number of intermediate cell compartments. We show that longer differentiation cascades are more prone to extinction than systems with less intermediate compartments. Furthermore, we have analysed the possibility of mixed symmetric and asymmetric cell division against invasions by mutant invaders in order to find optimal architecture. Our results show that more robust populations are those with unfrequent symmetric behaviour.     

Magnetic field and dissipation effects on the charge polarization in quantum cellular automata

We study the dynamic evolution of the charge distribution (polarization) of a 2/spl times/2 quantum-dot cell with two electrons in the presence of a time-dependent driver cell and a magnetic field. We describe the effects of the magnetic flux on the response of the basic dot cell, for fixed, and linear switching of the driver polarization. In the static case, we find that the magnetic field has a strong localizing effect, similar to the effect of asymmetry. For fixed tunneling, the polarization of the target cell increases with magnetic field, going through a maximum at a particular value of the magnetic flux through the cell. In the dynamic case, a ringing effect and a decrease in the final polarization value of the target cell are obtained as the magnetic field increases. The effects of temperature and asymmetry on these results are also analyzed.     

Cell Mechanical and Physiological Behavior in the Regime of Rapid Mechanical Compressions that Lead to Cell Volume Change

Cells respond to mechanical forces by deforming in accordance with viscoelastic solid behavior. Studies of microscale cell deformation observed by high speed video microscopy have elucidated a new cell behavior in which sufficiently rapid mechanical compression of cells can lead to transient cell volume loss and then recovery. This work has discovered that the resulting volume exchange between the cell interior and the surrounding fluid can be utilized for efficient, convective delivery of large macromolecules (2000 kDa) to the cell interior. However, many fundamental questions remain about this cell behavior, including the range of deformation time scales that result in cell volume loss and the physiological effects experienced by the cell. In this study, a relationship is established between cell viscoelastic properties and the inertial forces imposed on the cell that serves as a predictor of cell volume loss across human cell types. It is determined that cells maintain nuclear envelope integrity and demonstrate low protein loss after the volume exchange process. These results define a highly controlled cell volume exchange mechanism for intracellular delivery of large macromolecules that maintains cell viability and function for invaluable downstream research and clinical applications.     

Thyroid-Friendly Soft Materials as 3D Cell Culture Tool for Stimulating Thyroid Cell Function

The disruption of thyroid hormones because of chemical exposure is a significant societal problem. Chemical evaluations of environmental and human health risks are conventionally based on animal experiments. However, owing to recent breakthroughs in biotechnology, the potential toxicity of chemicals can now be evaluated using 3D cell cultures. In this study, the interactive effects of thyroid-friendly soft (TS) microspheres on thyroid cell aggregates are elucidated and their potential as a reliable toxicity assessment tool is evaluated. Using state-of-the-art characterization methods coupled with cell-based analysis and quadrupole time-of-flight mass spectrometry, it is shown that TS-microsphere-integrated thyroid cell aggregates exhibit improved thyroid function. Specifically, the responses of zebrafish embryos, which are used for thyroid toxicity analysis, and the TS-microsphere-integrated cell aggregates to methimazole (MMI), a known thyroid inhibitor, are compared. The results show that the thyroid hormone disruption response of the TS-microsphere-integrated thyroid cell aggregates to MMI is more sensitive compared with those of the zebrafish embryos and conventionally formed cell aggregates. This proof-of-concept approach can be used to control cellular function in the desired direction and hence evaluate thyroid function. Thus, the proposed TS-microsphere-integrated cell aggregates may yield new fundamental insights for advancing in vitro cell-based research.     

The interplay of cell–cell and cell–substrate adhesion in collective cell migration

Collective cell migration often involves notable cell–cell and cell–substrate adhesions and highly coordinated motion of touching cells. We focus on the interplay between cell–substrate adhesion and cell–cell adhesion. We show that the loss of cell-surface contact does not significantly alter the dynamic pattern of protrusions and retractions of fast migrating amoeboid cells (Dictyostelium discoideum), but significantly changes their ability to adhere to other cells. Analysis of the dynamics of cell shapes reveals that cells that are adherent to a surface may coordinate their motion with neighbouring cells through protrusion waves that travel across cell–cell contacts. However, while shape waves exist if cells are detached from surfaces, they do not couple cell to cell. In addition, our investigation of actin polymerization indicates that loss of cell-surface adhesion changes actin polymerization at cell–cell contacts. To further investigate cell–cell/cell–substrate interactions, we used optical micromanipulation to form cell–substrate contact at controlled locations. We find that both cell-shape dynamics and cytoskeletal activity respond rapidly to the formation of cell–substrate contact.     

Tailoring Biomaterials for Cancer Immunotherapy: Emerging Trends and Future Outlook

Cancer immunotherapy, as a paradigm shift in cancer treatment, has recently received tremendous attention. The active cancer vaccination, immune checkpoint blockage (ICB) and chimeric antigen receptor (CAR) for T‐cell‐based adoptive cell transfer are among these developments that have achieved a significant increase in patient survival in clinical trials. Despite these advancements, emerging research at the interdisciplinary interface of cancer biology, immunology, bioengineering, and materials science is important to further enhance the therapeutic benefits and reduce side effects. Here, an overview of the latest studies on engineering biomaterials for the enhancement of anticancer immunity is given, including the perspectives of delivery of immunomodulatory therapeutics, engineering immune cells, and constructing immune‐modulating scaffolds. The opportunities and challenges in this field are also discussed.     

植物纤维多孔材料泡孔分布影响因素

目的分析影响植物纤维多孔材料泡孔分布的各种因素,探究泡孔结构对性能的影响,为制备泡孔均匀分布、缓冲性能良好的多孔材料提供理论基础。方法归纳总结国内外植物纤维多孔材料泡孔结构的研究进展,探讨多孔材料的发泡机理,系统地阐述成型工艺、助剂种类、助剂含量等对植物纤维多孔材料泡孔结构的影响。结果通过分析得出各种影响因素的作用规律,为进一步完善植物纤维多孔材料的制备方案,开发泡孔分布均匀、性能稳定的植物纤维发泡材料提供依据。结论通过制定科学的实验方案,可以制备出泡孔分布均匀的多孔材料,其可作为缓冲材料,在包装领域中有巨大的市场需求。     

Preparation of Al-doped ZnO thin films as transparent conductive substrate in dye-sensitized solar cell

We have prepared aluminum-doped Zinc oxide (AZO) thin films on glass substrates by rf magnetron sputtering technique using ZnO ceramic target in pure argon gas with different aluminum concentrations. The bandgap of the ZnO films slightly widens with increase in Al content and the lowest sheet resistance of AZO films with Al concentration of 4.3 at.% was obtained. The effects of post-annealing treatment on structural, electrical and optical properties of the AZO thin films were investigated. Using AZO thin film with 4.3 at.% Al as the transparent substrate, a titanium dioxide based dye-sensitized solar cell was constructed and a solar to electrical energy conversion efficiency of 2.9% was achieved under AM 1.5 solar simulated sunlight.     

How to carry out assembly line–cell conversion? A discussion based on factor analysis of system performance improvements

The line–cell (or line–seru) conversion is an innovation of assembly systems that has received less attention. Its essence is dismantling an assembly conveyor line and adopting a mini-assembly unit, called seru (or cell). In this paper, we discuss how to do such line–cell conversions, especially focusing on assembly cell formation (ACF) and assembly cell loading (ACL). We perform 64 arrays of full factorial experiment analysis that incorporate three factors: work stations, product types, and product lot sizes. We construct a two-objective line–cell conversion model that minimises the total throughput time (TTPT) and the total labour hours (TLH). Three non-dominated solutions obtained from the two-objective model are used to evaluate the performance of the line–cell conversion. By investigating the experimental results of the ACF and the ACL, we summarise several managerial insights that could be used to help successful line–cell conversions.     

Effective Labeling of Primary Somatic Stem Cells with BaTiO3 Nanocrystals for Second Harmonic Generation Imaging

While nanoparticles are an increasingly popular choice for labeling and tracking stem cells in biomedical applications such as cell therapy, their intracellular fate and subsequent effect on stem cell differentiation remain elusive. To establish an effective stem cell labeling strategy, the intracellular nanocrystal concentration should be minimized to avoid adverse effects, without compromising the intensity and persistence of the signal necessary for long‐term tracking. Here, the use of second‐harmonic generating barium titanate nanocrystals is reported, whose achievable brightness allows for high contrast stem cell labeling with at least one order of magnitude lower intracellular nanocrystals than previously reported. Their long‐term photostability enables to investigate quantitatively at the single cell level their cellular fate in hematopoietic stem cells (HSCs) using both multiphoton and electron microscopy. It is found that the concentration of nanocrystals in proliferative multipotent progenitors is over 2.5‐fold greater compared to quiescent stem cells; this difference vanishes when HSCs enter a nonquiescent, proliferative state, while their potency remains unaffected. Understanding the nanoparticle stem cell interaction allows to establish an effective and safe nanoparticle labeling strategy into somatic stem cells that can critically contribute to an understanding of their in vivo therapeutic potential.     

SERS microscopic imaging as novel tool for assessing viability and enumerating yeast cells at various stages of cell cycle in lag,log, exponential and stationary phases of growth in culture

Surface enhanced Raman scattering (SERS) microscopic imaging was employed to enumerate the yeast cells in culture. We found this imaging method as an efficient tool for easily differentiating and quantitatively enumerating yeast cell at different stages of cell-division cycle (G1, S, G2 and M phase) at various stages of growth phases namely lag, log, exponential and stationary phases in culture. Apart from enumerating the cells at different stages of cell cycle under lag, log, exponential and stationary phases, it was possible using SERS microscopy to differentiate the live cells from dead ones. The dead cells were SERS inactive and gave enhanced autofluorescence compared with the live cells, which were SERS active. The results from the present investigation suggest that SERS microscopic imaging, using silver nanoparticles (AgNPs) as a sensitive tool to enumerate the yeast cells in culture.     

Effect of process conditions on dynamics and performance of PEMFC: Comparison with experiments

Three-dimensional numerical computations have been carried out to investigate the dynamics inside proton-exchange membrane fuel cell (PEMFC) and its performance using Star-CD solver, the computational fluid dynamics software. Theoretical results in polarization curves quantitatively corroborate the experimental findings previously reported in Jung et al. [2]. Also, effects of various process conditions such as relative humidity, stoichiometric ratio at anode and cathode channels, and cell configuration on the performance of fuel cell have been further scrutinized. It has been revealed that the moderately high stoichiometric ratio at cathode channel and single serpentine geometry improve the cell performance and also the humidity change at cathode makes the cell voltage variation high, comparing with the humidity change at anode.     

Decoupling the Direct and Indirect Biological Effects of ZnO Nanoparticles Using a Communicative Dual Cell‐Type Tissue Construct

While matter at the nanoscale can be manipulated, the knowledge of the interactions between these nanoproducts and the biological systems remained relatively laggard. Current nanobiology study is rooted on in vitro study using conventional 2D cell culture model. A typical study employs monolayer cell culture that simplifies the real context of which to measure any nanomaterial effect; unfortunately, this simplification also demonstrated the limitations of 2D cell culture in predicting the actual biological response of some tissues. In fact, some of the characteristics of tissue such as spatial arrangement of cells and cell–cell interaction, which are simplified in 2D cell culture model, play important roles in how cells respond to a stimulus. To more accurately recapitulate the features and microenvironment of tissue for nanotoxicity assessments, an improved organotypic‐like in vitro multicell culture system to mimic the kidney endoepithelial bilayer is introduced. Results showed that important nano‐related parameters such as the diffusion, direct and indirect toxic effects of ZnO nanoparticles can be studied by combining this endoepithelial bilayer tissue model and traditional monolayer culture setting.