Themed collection Integrative Biology Recent HOT Articles

A combined approach involving microfluidic pulsatile stimulation and mathematical modeling has led to deciphering of hidden/unknown temporal motifs in several mammalian signaling pathways and has provided mechanistic insights, including how these motifs process temporal signals and govern fate regulation.

Organ-on-a-chip and organoid culture models present complementary approaches in studying development and disease by balancing experimental tractability and the ability to mimic physiological complexity.

We present various exciting examples of synthetic biology as a means to distill biological systems to their essential features in order to make them theoretically tractable.

Synthetic biology builds new systems not only for applications but also to understand biology, achieving fundamental insights in the process.

Synthetic biology, an engineering, circuit-driven approach to biology, has developed whole new classes of tools that can be used together to create novel mock systems, fine-tuned in vivo reporters, spatially and temporally inducible models and closed-loop systems often leading to previously unattainable biological insights.

In this review we discuss how synthetic biology facilitates the task of investigating genetic circuits that are observed in naturally occurring biological systems.

A systems biology model of VEGF–TSP1 network in cancer patients generates insights into the heterogeneous response to combination anti-angiogenic therapy.

Landscapes for random parameter perturbation reveal the operating principles of gene networks.

We used a multiscale systems pharmacology model to provide insight into the mechanisms of action of several classes of pro-angiogenic therapies.

Drug response screening, gene expression, and kinome signaling were combined across biomaterial platforms to combat adaptive resistance to sorafenib.

Early expression of RIG-I and MDA5 in a subset of infected cells may contribute to the decision making process for turning on the IFNB1 expression.

Overlapping arrays of microfluidic channels deliver gentle and harsh touch stimuli to multiple C. elegans, revealing factors that influence their response decisions.

Synthetic 3D matrix binds cell-secreted matrix and mimics endometrial epithelial–stromal tissue architecture, hormone responsiveness, and cytokine production.

Hyaluronan, CD44 and the Receptor for Hyaluronan-Mediated Motility (RHAMM, gene name HMMR) regulate stem cell differentiation including mesenchymal progenitor differentiation.

A novel microsphere-based flow cytometry approach to study adherent cell signaling responses in different microenvironmental contexts at the single cell level.

This simple device employs an elastic substrate to pattern a sharp border between two adjoining cell populations.

The simultaneous measurement of T cell function with recovery of individual T cells would greatly facilitate characterizing antigen-specific responses both in vivo and in model systems.

A combinatorial cell microarray platform to map the impact of both extracellular matrix proteins and genotype on the drug responses of tumor cells.

α-Ketoglutarate substrate inhibition kinetics of hepatic glutamate dehydrogenase amination activity confers robust control over the ratio between glutamate and ammonium.

This study integrates mechanics and neuroscience to model the mechanoelectrochemical transduction of vibrations into neural signals in the Pacinian corpuscle.

Nanoscale tension gauges revealed how substrate stiffness alters pico Newton force thresholds that trigger initial cell attachment, spreading, and adhesion maturation.

Large-scale arrays of transcription factor activity reveal differential responses to chemical and mechanical aspects of the extracellular environment.

Fiber alignment within tumor-mimetic engineered collagen matrices drives FAK- and Rac1-dependent cellular anisotropy that promotes protrusions along fibers and suppresses off-axis protrusions to direct cell migration.

PDMS microwell platforms provide an innovative approach to better characterize the dynamics of metabolic activities in single mitochondria within a population.

We demonstrated in a microfluidic system that initiation of clotting of flowing human whole blood overcomes a patch threshold response to stimuli patch size when tissue factor and von Willebrand factor are present.

Adhesive micropatterns have become a standard tool to control cell shape and function in cell culture.

A microwell system for detection of secreted products from adherent cells is used to demonstrate that macrophage adhesive context and cell shape regulate cytokine secretion and population heterogeneity.

Vinculin head–tail interaction regulates rigidity-dependent cell branching and recruitment of talin, but not of paxillin or FAK.

Total internal reflection fluorescence microscopy (TIRF) and Qdot probe based analytical method for the simultaneous evaluation of the cytotoxic ability of camptothecin and the drug resistance profile upon the inhibition of drug efflux pumps in breast cancer stem cells.

Germination of a population of pathogenic fungal spores into yeast can be tracked, quantified, and parsed using a microfluidic assay.

Bidirectional coupling between a synthetic oscillator and the bacterial cell cycle leads to their mutual entrainment.

Concentration of viable cell populations in suspension is of interest for several clinical and pre-clinical applications.

Consistently-biased left–right (LR) patterning is required for the proper placement of organs including the heart and viscera.

Artificial antigen presenting cells with clustered T cell ligands were prepared and used to reveal a dual scale of T cell response: a local nano-scale response in which the cell redistributes key signalling molecules, and a global cell scale response according to the average ligand density.

This work identifies the molecular mechanisms by which interstitial fluid pressure drives collective invasion in an engineered model of solid human tumors.

A spheroid-based in vitro 3D ALD model with perfusion culture can establish the reversible and irreversible states of ALD.

Inositol hexakisphosphate (InsP₆ or IP₆) is an important signalling molecule. An IP₆ probe was synthesised from myo-inositol and immobilised onto Dynabeads for proteomic analysis. LC/MS/MS analysis identified 77 proteins or protein complexes that bind to IP₆ specifically.

Can we control the photosensitized production of intracellular singlet oxygen?

A cell mixer microbioreactor array platform that permits the rapid establishment of perfused cell co-culture models in a high-throughput, programmable fashion.

Mathematical modeling of plasticity expressed in EMT undergoing HaCaT cell population endorsed with molecular expressions and phenotype morphometry.

We show that the trapping of neutrophil-derived chromatin fibres at the entrance of microchannel networks in vitro can result in the formation of disproportionately large areas with no RBC traffic.

Development of a biofunctionalized three-dimensional hydrogel scaffold for hepatoctye cell culture highlights the importance of cell morphology, more specifically sheet-layer formation, in regulating gene expression.

We engineered novel electrospun protein fabrics to gain insight into cellular responses to heterogeneity in global versus local ligand density.

A microdevice to model type 2 diabetes-like hyperglycemia in C. elegans and examine several aspects of this disease in C. elegans.

Micro-scale topography mimics stem cell patterning in human interfollicular epidermal stem cells.

This study demonstrates the use of a novel high frequency acoustic nebulisation platform as an effective aerosolisation technique for inhaled mesenchymal stem cell (MSC) therapy.

We present a microfluidic gradient generator that exposes cultured cells to orthogonally-aligned linear concentration gradients of two molecules. Live-cell assays quantifying apoptotic signaling and cell motility are provided as proof-of-concept.

Chemical imaging of single cells at the molecular level is important in capturing biological dynamics.

Simultaneous analysis of the production of reactive oxygen species and formation of extracellular traps from neutrophils isolated from a drop of blood using a novel microfluidics based approach.