
New insights into mammalian signaling pathways using microfluidic pulsatile inputs and mathematical modeling
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.
Integr. Biol., 2017,9, 6-21
http://dx.doi.org/10.1039/C6IB00178E
Three-dimensional models for studying development and disease: moving on from organisms to organs-on-a-chip and organoids
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.
Integr. Biol., 2016,8, 672-683
http://dx.doi.org/10.1039/C6IB00039H
Using synthetic biology to make cells tomorrow's test tubes
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.
Integr. Biol., 2016,8, 431-450
http://dx.doi.org/10.1039/C6IB00006A
From noise to synthetic nucleoli: can synthetic biology achieve new insights?
Synthetic biology builds new systems not only for applications but also to understand biology, achieving fundamental insights in the process.
Integr. Biol., 2016,8, 383-393
http://dx.doi.org/10.1039/C5IB00271K
Synthetic biology: applying biological circuits beyond novel therapies
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.
Integr. Biol., 2016,8, 409-430
http://dx.doi.org/10.1039/C5IB00263J
Build to understand: synthetic approaches to biology
In this review we discuss how synthetic biology facilitates the task of investigating genetic circuits that are observed in naturally occurring biological systems.
Integr. Biol., 2016,8, 394-408
http://dx.doi.org/10.1039/C5IB00252D

The impact of tumor receptor heterogeneity on the response to anti-angiogenic cancer treatment
A systems biology model of VEGF–TSP1 network in cancer patients generates insights into the heterogeneous response to combination anti-angiogenic therapy.
Integr. Biol., 2018, Advance Article
http://dx.doi.org/10.1039/C8IB00019K
Landscape of gene networks for random parameter perturbation
Landscapes for random parameter perturbation reveal the operating principles of gene networks.
Integr. Biol., 2018,10, 92-99
http://dx.doi.org/10.1039/C7IB00198C
A computational analysis of pro-angiogenic therapies for peripheral artery disease
We used a multiscale systems pharmacology model to provide insight into the mechanisms of action of several classes of pro-angiogenic therapies.
Integr. Biol., 2018,10, 18-33
http://dx.doi.org/10.1039/C7IB00218A
A biomaterial screening approach reveals microenvironmental mechanisms of drug resistance
Drug response screening, gene expression, and kinome signaling were combined across biomaterial platforms to combat adaptive resistance to sorafenib.
Integr. Biol., 2017,9, 912-924
http://dx.doi.org/10.1039/C7IB00128B
Single-cell analysis of early antiviral gene expression reveals a determinant of stochastic IFNB1 expression
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.
Integr. Biol., 2017,9, 857-867
http://dx.doi.org/10.1039/C7IB00146K
Comparing Caenorhabditis elegans gentle and harsh touch response behavior using a multiplexed hydraulic microfluidic device
Overlapping arrays of microfluidic channels deliver gentle and harsh touch stimuli to multiple C. elegans, revealing factors that influence their response decisions.
Integr. Biol., 2017,9, 800-809
http://dx.doi.org/10.1039/C7IB00120G
Local remodeling of synthetic extracellular matrix microenvironments by co-cultured endometrial epithelial and stromal cells enables long-term dynamic physiological function
Synthetic 3D matrix binds cell-secreted matrix and mimics endometrial epithelial–stromal tissue architecture, hormone responsiveness, and cytokine production.
Integr. Biol., 2017,9, 271-289
http://dx.doi.org/10.1039/C6IB00245E
Receptor for hyaluronan mediated motility (RHAMM/HMMR) is a novel target for promoting subcutaneous adipogenesis
Hyaluronan, CD44 and the Receptor for Hyaluronan-Mediated Motility (RHAMM, gene name HMMR) regulate stem cell differentiation including mesenchymal progenitor differentiation.
Integr. Biol., 2017,9, 223-237
http://dx.doi.org/10.1039/C7IB00002B
Microsphere cytometry to interrogate microenvironment-dependent cell signaling
A novel microsphere-based flow cytometry approach to study adherent cell signaling responses in different microenvironmental contexts at the single cell level.
Integr. Biol., 2017,9, 123-134
http://dx.doi.org/10.1039/C6IB00207B
Patterning of sharp cellular interfaces with a reconfigurable elastic substrate
This simple device employs an elastic substrate to pattern a sharp border between two adjoining cell populations.
Integr. Biol., 2017,9, 50-57
http://dx.doi.org/10.1039/C6IB00203J
Identification and isolation of antigen-specific cytotoxic T lymphocytes with an automated microraft sorting system
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.
Integr. Biol., 2016,8, 1208-1220
http://dx.doi.org/10.1039/C6IB00168H
Mapping lung tumor cell drug responses as a function of matrix context and genotype using cell microarrays
A combinatorial cell microarray platform to map the impact of both extracellular matrix proteins and genotype on the drug responses of tumor cells.
Integr. Biol., 2016,8, 1221-1231
http://dx.doi.org/10.1039/C6IB00179C
Robust regulation of hepatic pericentral amination by glutamate dehydrogenase kinetics
α-Ketoglutarate substrate inhibition kinetics of hepatic glutamate dehydrogenase amination activity confers robust control over the ratio between glutamate and ammonium.
Integr. Biol., 2016,8, 1126-1132
http://dx.doi.org/10.1039/C6IB00158K
A multiphysics model of the Pacinian corpuscle
This study integrates mechanics and neuroscience to model the mechanoelectrochemical transduction of vibrations into neural signals in the Pacinian corpuscle.
Integr. Biol., 2016,8, 1111-1125
http://dx.doi.org/10.1039/C6IB00157B
Nanoscale mechanics guides cellular decision making
Nanoscale tension gauges revealed how substrate stiffness alters pico Newton force thresholds that trigger initial cell attachment, spreading, and adhesion maturation.
Integr. Biol., 2016,8, 929-935
http://dx.doi.org/10.1039/C6IB00113K
Dynamic transcription factor activity networks in response to independently altered mechanical and adhesive microenvironmental cues
Large-scale arrays of transcription factor activity reveal differential responses to chemical and mechanical aspects of the extracellular environment.
Integr. Biol., 2016,8, 844-860
http://dx.doi.org/10.1039/C6IB00093B
Local extracellular matrix alignment directs cellular protrusion dynamics and migration through Rac1 and FAK
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.
Integr. Biol., 2016,8, 821-835
http://dx.doi.org/10.1039/C6IB00030D
PDMS microwells for multi-parametric monitoring of single mitochondria on a large scale: a study of their individual membrane potential and endogenous NADH
PDMS microwell platforms provide an innovative approach to better characterize the dynamics of metabolic activities in single mitochondria within a population.
Integr. Biol., 2016,8, 836-843
http://dx.doi.org/10.1039/C6IB00064A
Minimum wound size for clotting: flowing blood coagulates on a single collagen fiber presenting tissue factor and von Willebrand factor
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.
Integr. Biol., 2016,8, 813-820
http://dx.doi.org/10.1039/C6IB00077K
Optimizing micropattern geometries for cell shape and migration with genetic algorithms
Adhesive micropatterns have become a standard tool to control cell shape and function in cell culture.
Integr. Biol., 2016,8, 741-750
http://dx.doi.org/10.1039/C6IB00061D
Macrophage secretion heterogeneity in engineered microenvironments revealed using a microwell platform
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.
Integr. Biol., 2016,8, 751-760
http://dx.doi.org/10.1039/C6IB00053C

Vinculin head–tail interaction defines multiple early mechanisms for cell substrate rigidity sensing
Vinculin head–tail interaction regulates rigidity-dependent cell branching and recruitment of talin, but not of paxillin or FAK.
Integr. Biol., 2016,8, 693-703
http://dx.doi.org/10.1039/C5IB00307E
Quantitative evaluation of ABC transporter-mediated drug resistance based on the determination of the anticancer activity of camptothecin against breast cancer stem cells using TIRF
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.
Integr. Biol., 2016,8, 704-711
http://dx.doi.org/10.1039/C6IB00021E
Leveraging a high resolution microfluidic assay reveals insights into pathogenic fungal spore germination
Germination of a population of pathogenic fungal spores into yeast can be tracked, quantified, and parsed using a microfluidic assay.
Integr. Biol., 2016,8, 603-615
http://dx.doi.org/10.1039/C6IB00012F
Mutual regulation causes co-entrainment between a synthetic oscillator and the bacterial cell cycle
Bidirectional coupling between a synthetic oscillator and the bacterial cell cycle leads to their mutual entrainment.
Integr. Biol., 2016,8, 533-541
http://dx.doi.org/10.1039/C5IB00262A

Label-free concentration of viable neurons, hESCs and cancer cells by means of acoustophoresis
Concentration of viable cell populations in suspension is of interest for several clinical and pre-clinical applications.
Integr. Biol., 2016,8, 332-340
http://dx.doi.org/10.1039/C5IB00288E
Conserved roles for cytoskeletal components in determining laterality
Consistently-biased left–right (LR) patterning is required for the proper placement of organs including the heart and viscera.
Integr. Biol., 2016,8, 267-286
http://dx.doi.org/10.1039/C5IB00281H
Nano-clustering of ligands on surrogate antigen presenting cells modulates T cell membrane adhesion and organization
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.
Integr. Biol., 2016,8, 287-301
http://dx.doi.org/10.1039/C5IB00293A
Interstitial fluid pressure regulates collective invasion in engineered human breast tumors via Snail, vimentin, and E-cadherin
This work identifies the molecular mechanisms by which interstitial fluid pressure drives collective invasion in an engineered model of solid human tumors.
Integr. Biol., 2016,8, 319-331
http://dx.doi.org/10.1039/C5IB00282F
A 3D alcoholic liver disease model on a chip
A spheroid-based in vitro 3D ALD model with perfusion culture can establish the reversible and irreversible states of ALD.
Integr. Biol., 2016,8, 302-308
http://dx.doi.org/10.1039/C5IB00298B
Synthesis of an inositol hexakisphosphate (IP6) affinity probe to study the interactome from a colon cancer cell line
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.
Integr. Biol., 2016,8, 309-318
http://dx.doi.org/10.1039/C5IB00264H
Intracellular singlet oxygen photosensitizers: on the road to solving the problems of sensitizer degradation, bleaching and relocalization
Can we control the photosensitized production of intracellular singlet oxygen?
Integr. Biol., 2016,8, 177-193
http://dx.doi.org/10.1039/C5IB00295H
Stoichiometric control of live cell mixing to enable fluidically-encoded co-culture models in perfused microbioreactor arrays
A cell mixer microbioreactor array platform that permits the rapid establishment of perfused cell co-culture models in a high-throughput, programmable fashion.
Integr. Biol., 2016,8, 194-204
http://dx.doi.org/10.1039/C5IB00311C
Modeling continuum of epithelial mesenchymal transition plasticity
Mathematical modeling of plasticity expressed in EMT undergoing HaCaT cell population endorsed with molecular expressions and phenotype morphometry.
Integr. Biol., 2016,8, 167-176
http://dx.doi.org/10.1039/C5IB00219B
Capillary plexuses are vulnerable to neutrophil extracellular traps
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.
Integr. Biol., 2016,8, 149-155
http://dx.doi.org/10.1039/C5IB00265F
Phenotypic regulation of liver cells in a biofunctionalized three-dimensional hydrogel platform
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.
Integr. Biol., 2016,8, 156-166
http://dx.doi.org/10.1039/C5IB00269A
Use of protein-engineered fabrics to identify design rules for integrin ligand clustering in biomaterials
We engineered novel electrospun protein fabrics to gain insight into cellular responses to heterogeneity in global versus local ligand density.
Integr. Biol., 2016,8, 50-61
http://dx.doi.org/10.1039/C5IB00258C
Modeling type 2 diabetes-like hyperglycemia in C. elegans on a microdevice
A microdevice to model type 2 diabetes-like hyperglycemia in C. elegans and examine several aspects of this disease in C. elegans.
Integr. Biol., 2016,8, 30-38
http://dx.doi.org/10.1039/C5IB00243E

Mimicking the topography of the epidermal–dermal interface with elastomer substrates
Micro-scale topography mimics stem cell patterning in human interfollicular epidermal stem cells.
Integr. Biol., 2016,8, 21-29
http://dx.doi.org/10.1039/C5IB00238A
Assessment of the potential of a high frequency acoustomicrofluidic nebulisation platform for inhaled stem cell therapy
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.
Integr. Biol., 2016,8, 12-20
http://dx.doi.org/10.1039/C5IB00206K
A microfluidic dual gradient generator for conducting cell-based drug combination assays
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.
Integr. Biol., 2016,8, 39-49
http://dx.doi.org/10.1039/C5IB00209E
Chemical imaging of molecular changes in a hydrated single cell by dynamic secondary ion mass spectrometry and super-resolution microscopy
Chemical imaging of single cells at the molecular level is important in capturing biological dynamics.
Integr. Biol., 2016,8, 635-644
http://dx.doi.org/10.1039/C5IB00308C
Microfluidic device for simultaneous analysis of neutrophil extracellular traps and production of reactive oxygen species
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.
Integr. Biol., 2016,8, 243-252
http://dx.doi.org/10.1039/C5IB00225G
About this collection
Here is a collection of recent Integrative Biology articles which have been classified as ‘HOT articles’ due to receiving particularly high scores at peer review.