The present study delineates the fabrication of paper-based devices for culturing liver cells and developing related bioassays. The devices were prepared by conventional lab-based LaserJet printing technology and employed for 3D cell culture. Our results demonstrated that the devices efficiently supported the growth of multiple cell types incuding HepG2, HUVEC, fibroblasts, and MSCs. We further showed that the device specifications (grade of paper or design parameters) greatly impacted the functional phenotype of the HepG2 cells. We also explored the application of the developed devices for routine cell culture, drug screening, coculture, and transwell migration assays. The cellular responses observed on the paper under different culture configurations were similar to those obtained in the case of tissue culture plate (TCP). Moreover, we showed that the paper-based devices were compatible with the immunocytochemistry and ELISA procedures (no indication of nonspecific matrix-antibody interaction). Considering the simplicity, experimental flexibility, cost-effectiveness, and multiplexibility of the paper-based liver models, it is deemed to be ideal for developing cell-based bioassays, especially in resource-limited settings.

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Noise in expression of individual genes gives rise to variations in activity of cellular pathways and generates heterogeneity in cellular phenotypes. Phenotypic heterogeneity has important implications for antibiotic persistence, mutation penetrance, cancer growth and therapy resistance. Specific molecular features such as the presence of the TATA box sequence and the promoter nucleosome occupancy have been associated with noise. However, the relative importance of these features in noise regulation is unclear and how well these features can predict noise has not yet been assessed. Here through an integrated statistical model of gene expression noise in yeast we found that the number of regulating transcription factors (TFs) of a gene was a key predictor of noise, whereas presence of the TATA box and the promoter nucleosome occupancy had poor predictive power. With an increase in the number of regulatory TFs, there was a rise in the number of cooperatively binding TFs. In addition, an increased number of regulatory TFs meant more overlaps in TF binding sites, resulting in competition between TFs for binding to the same region of the promoter. Through modeling of TF binding to promoter and application of stochastic simulations, we demonstrated that competition and cooperation among TFs could increase noise. Thus, our work uncovers a process of noise regulation that arises out of the dynamics of gene regulation and is not dependent on any specific transcription factor or specific promoter sequence.

Degree of oxygenation is one of the important parameters governing various processes, including cell proliferation, angiogenesis, extracellular matrix production, and even combating the microbial burden at the wound site, all...

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