The precise regulation of fundamental cellular behaviors, such as cell adhesion, proliferation, migration, differentiation, and cell-cell interactions, is essential in multicellular organisms. The regulation of cellular behaviors largely relies on the receptor-mediated sensing and transduction of the extracellular ligands. The precise manipulation of ligand-induced receptor activation via molecular engineering approaches will offer fundamental insight into physiological processes, facilitating the rational design of cell-based therapeutics to treat diseases. DNA is a highly attractive biomolecule as it works through either genetically encoding the functional protein or rationally fabricating functional nanomaterials. Recently accumulated research in functional nucleic acids and DNA nanotechnology makes it possible to construct dynamic and complex nanodevices to modulate receptor-mediated signaling and cellular behaviors. This review summarizes the recent advances in state-of-art of DNA technologies in engineering the interaction between ligand and cell-surface receptor, mainly highlighting the design principles and the emerging applications of DNA-based nongenetic engineering strategies for receptor-mediated cellular behaviors. We expect that significant advancements in DNA-based engineering strategies will enable the emergence of applications in cell-based therapy in regenerative medicine and cancer immunotherapy.

Biophysical properties of the extracellular environment dynamically regulate cellular fates. In this review, we highlight silk, an indispensable polymeric biomaterial, owing to its unique mechanical properties, bioactive component sequestration, degradability, well-defined architectures, and biocompatibility that can regulate temporospatial biochemical and biophysical responses. We explore how the materiobiology of silks, both mulberry and non-mulberry based, affect cell behaviors including cell adhesion, cell proliferation, cell migration, and cell differentiation. Keeping in mind the novel biophysical properties of silk in film, fiber, or sponge forms, coupled with facile chemical decoration, and its ability to match functional requirements for specific tissues, we survey the influence of composition, mechanical properties, topography, and 3D geometry in unlocking the body\'s inherent regenerative potential.

Electrospun fiber scaffolds, due to their mimicry of bone extracellular matrix (ECM), have become an important biomaterial widely applied in bone tissue engineering in recent years. While topographic cues of electrospun membranes such as alignment and diameter played vital roles in determining cellular behaviors. Yet few researches about the effects of these two significant parameters on osteogenesis have been reported. Thus, the present work explored the influence of aligned and random poly (L-lactic acid) (PLLA) fiber matrices with diameters of nanoscale (0.6 μm) and microscale (1.2 μm), respectively, on cellular responses of bone marrow mesenchymal stem cells (BMSCs), such as cell adhesion, migration, proliferation and osteogenesis. Our results revealed that aligned nanofibers (AN) could affect cell morphology and promote the migration of BMSCs after 24 h of cell culturing. Besides, AN group was observed to possess excellent biocompatibility and have significantly improved cell growth comparing with random nanofibers. More importantly, in vitro osteogenesis researches including ALP and Alizarin Red S staining, qRT-PCR and immunofluorescence staining demonstrated that BMSCs culturing on AN group exhibited higher osteogenic induction proficiency than that on aligned microfibers (AM) and random fiber substrates (RN and RM). Accordingly, aligned nanofiber scaffolds have greater application potential in bone tissue engineering.

The grain structure and surface morphology of bio-implants act as a pivotal part in altering cell behavior. Titanium alloy bone screws, as common implants, are prone to screws loosening and complications threat in the physiological environment due to their inferior anti-wear and surface inertia. Manufacturing bone screws with high wear resistance and ideal biocompatibility has always been a challenge. In this study, a series of overlapping morphologies inspired by the hierarchical structure of fish scales and micro bulges of shrimp were structured on Ti-6Al-4V implant by laser texturing. The results indicate that the textured patterns could improve cell attachment, proliferation, and osteogenic differentiation. The short-term response of human bone marrow-derived mesenchymal stem cells (hBMSCs) on the textured surface are more sensitive to the microstructure than the surface roughness, wettability, grain size and surface chemical elements of the textured surfaces. More importantly, the friction-increasing and friction-reducing type overlapping structures exhibit excellent friction stability at different stages of modified simulated body fluid (m-SBF) soaking. The overlapping structure (Micro-smooth stacked ring: MSSR) is more beneficial to promote the formation of apatite. Deposited spherical-like apatite particles can act as a \"lubricant\" on the MSSR surface during the friction process to alleviate the adhesion wear of the surface. Meanwhile, apatite particles participate in the formation of friction film, which plays an effective role in reducing friction and antiwear in corrosion solution (m-SBF) for a long time. These features show that the combination of soaking treatment in m-SBF solution with laser-textured MSSR structure is expected to be an efficient and environmentally friendly strategy to prolong the service life of bone screws and reducing the complications of mildly osteoporotic implants.

BACKGROUND: CHIP is an E3 ubiquitin ligase that plays contrast roles in diverse human malignancies, depending on its targets. To date, the mechanisms underlying the function of CHIP in gastric cancer remains unclear. Here, we aim to further clarify the effects of CHIP on the development and progression of gastric cancer and explore its potential target.
METHODS: Stably transfected CHIP-shRNA and TRAF2-shRNA AGS gastric cancer cell lines were established using Lipofectamine 2000. Cell growth was measured by an xCelligence real-time monitoring system and colony formation assay. Cell proliferation was detected using CCK-8, Ki-67, or CFSE assays. Apoptosis was detected by TUNEL assay or Annexin V/PI-staining followed by flow cytometric analysis. Cell cycle distribution was detected by PI-staining followed by flow cytometric analysis. Cell migration and invasion abilities were measured by a real-time xCelligence system, Transwell insert, and scratch assays. The expression of cell cycle-related proteins, apoptosis-related proteins, AKT, ERK, NF-κB signaling subunits, MMP2, MMP9, and Integrin β-1 were detected by Western blotting analysis. NF-κB DNA-binding capability was quantified using an ELISA-based NF-κB activity assay. Gastric cancer tissue microarray was analyzed to investigate the expression of both CHIP and TRAF2, and their clinical significance.
RESULTS: The CHIP-silencing in the AGS cells was oncogenic evidenced by the appearance of capable of anchorage-independent growth. The CHIP-silencing significantly enhanced the AGS cell proliferation capability likely due to the induced phosphorylation of ERK. The CHIP-silencing significantly inhibited apoptosis due to increased expression of Bcl-2. The CHIP-silencing promoted the AGS cell migration and invasion abilities, likely by regulating the expression of Integrin β-1. TRAF2 expression was markedly decreased in the CHIP-overexpressing cells at protein level, but not at mRNA level. The TRAF2-silencing markedly inhibited the proliferation ability of the AGS cells, the defected cell proliferation and enhanced apoptosis were involved in. The TRAF2-silencing also attenuated the cell migration and invasion capacities of the AGS cells. Furthermore, the expression of CHIP was downregulated while the expression of TRAF2 was upregulated in gastric cancer tissues. TRAF2 expression is independent prognostic factors of gastric cancer. The expression of CHIP and TRAF2 was negatively correlated in the gastric cancer tissue. Lower CHIP or higher TRAF2 was significantly linked to shorter overall survival in gastric cancer patients.
CONCLUSIONS: TRAF2 influenced diverse aspects of cellular behavior of gastric cancer cells, including cell growth, migration, and invasion, which was in contrast to the functions of CHIP. TRAF2 could be considered as an independent prognostic factor in gastric cancer patients. It is possible that TRAF2 was a substrate of CHIP and CHIP regulated the TRAF2/NF-κB axis, which modulated diverse cellular behaviors in the AGS gastric cancer cells.

We present an image-matching-based automated algorithm capable of accurately determining the self-rotational speed of cancer cells in an optically-induced electrokinetics-based microfluidic chip. To automatically track a specific cell in a video featuring more than one cell, a background subtraction technique was used. To determine the rotational speeds of cells, a reference frame was automatically selected and curve fitting was performed to improve the stability and accuracy. Results show that the algorithm was able to accurately calculate the self-rotational speeds of cells up to ~150 rpm. In addition, the algorithm could be used to determine the motion trajectories of the cells. Potential applications for the developed algorithm include the differentiation of cell morphology and characterization of cell electrical properties.

Biodegradable zinc (Zn) metals, a new generation of biomaterials, have attracted much attention due to their excellent biodegradability, bioabsorbability, and adaptability to tissue regeneration. Compared with magnesium (Mg) and iron (Fe), Zn exhibits better corrosion and mechanical behaviors in orthopedic and stent applications. After implantation, Zn containing material will slowly degrade, and Zn ions (Zn2+) will be released to the surrounding tissue. For stent applications, the local Zn2+concentration near endothelial tissue/cells could be high. However, it is unclear how endothelia will respond to such high concentrations of Zn2+, which is pivotal to vascular remodeling and regeneration. Here, we evaluated the short-term cellular behaviors of primary human coronary artery endothelial cells (HCECs) exposed to a concentration gradient (0-140 μM) of extracellular Zn2+. Zn2+ had an interesting biphasic effect on cell viability, proliferation, spreading, and migration. Generally, low concentrations of Zn2+ promoted viability, proliferation, adhesion, and migration, while high concentrations of Zn2+ had opposite effects. For gene expression profiles, the most affected functional genes were related to cell adhesion, cell injury, cell growth, angiogenesis, inflammation, vessel tone, and coagulation. These results provide helpful information and guidance for Zn-based alloy design as well as the controlled release of Zn2+in stent and other related medical applications.

The layer-by-layer (LbL) technique was introduced in the early 1990s. Since then, it has undergone a series of technological developments, making it possible to engineer various theranostic platforms, such as films and capsules, with precise control at the nanometer and micrometer scales. Recent progress in the applications of LbL assemblies in the field of cancer therapy, diagnosis, and fundamental biological study are highlighted here. The potential of LbL-based systems as drug carriers is discussed, especially with regard to the engineering of innovative stimuli-responsive systems, and their advantageous multifunctionality in the development of new therapeutic tools. Then, the diagnostic functions of LbL assemblies are illustrated for detection and capture of rare cancer cells. Finally, LbL-mimicking extracellular environments demonstrate the emerging potential for the study of cancer cell behavior in vitro. The advantages of LbL systems, important challenges that need to be overcome, and future perspectives in clinical practice are then highlighted.

New microscopic approaches, high-throughput imaging, and gene editing promise major new insights into cellular behaviors. When coupled with genomic and other \'omic information and \"mined\" for correlations and associations, a new breed of powerful and useful cellular models should emerge. These top down, coarse-grained, and statistical models, in turn, can be used to form hypotheses merging with fine-grained, bottom up mechanistic studies and models that are the back bone of cell biology. The goal of the Allen Institute for Cell Science is to develop the top down approach by developing a high throughput microscopy pipeline that is integrated with modeling, using gene edited hiPS cell lines in various physiological and pathological contexts. The output of these experiments and models will be an \"animated\" cell, capable of integrating and analyzing image data generated from experiments and models.

The adsorption of proteins, in particular fibronectin (Fn), was studied on poly(ethylene glycol) (PEG, 5kDa)-grafted surfaces, and was correlated with the adhesion behaviors of smooth muscle cells (SMCs). The PEG molecules were covalently grafted on aldehyde-activated substrates with different densities of amino groups. The thickness of PEG layer increased nearly 10 fold in a hydrated state, reaching to 27nm on the surface of highest PEG chain density with a brush configuration. On the lower PEG-grafted surfaces, however, the PEG molecules adopted a mushroom configuration. The adsorption of Fn without and with the competition of bovine serum albumin (BSA) and serum was studied by using ellipsometry, fluorescence microscopy and radio-labeling techniques. The adsorption amount of Fn in serum decreased initially with increased PEG chain density until 0.12chains/nm(2) PEG, and then slightly increased on the 0.29chains/nm(2) PEG. A series of protein preadsorption experiments were carried out under different conditions before SMCs culture in vitro. Compared with those substrates without Fn preadsorption, the cell adhesion and spreading were significantly enhanced on all the PEG surfaces preadsorbed with Fn and serum, although they overall decreased along with the increase of PEG grafting density. The adhesion force of Fn decreased monotonously with the increase of PEG grafting density, which was in accordance with the cell adhesion force. The correlation between the PEG-grafted surfaces, Fn adsorption, and cellular behaviors is finally suggested.