Long-range mechanical force in colony branching and tumor invasion

The most concerned factors for cancer prognosis are tumor invasion and metastasis. The patterns of tumor invasion can be characterized as random infiltration to surrounding extracellular matrix (ECM) or formation of long-range path for collective migration. Recent studies indicate that mechanical force plays an important role in tumor infiltration and collective migration. However, how tumor colonies develop mechanical interactions with each other to initiate various invasion patterns is unclear. Using a micro-patterning technique, we partition cells into clusters to mimic tumor colonies and quantitatively induce colony-ECM interactions. We find that pre-malignant epithelial cells, in response to concentrations of type I collagen in ECM ([COL]), develop various branching patterns resembling those observed in tumor invasion. In contrast with conventional thought, these patterns require long-range (~ 600 μm) transmission of traction force, but not biochemical factors. At low [COL], cell colonies synergistically develop pairwise and directed branching mimicking the formation of long-range path. By contrast, at high [COL] or high colony density, cell colonies develop random branching and scattering patterns independent of each other. Our results suggest that tumor colonies might select different invasive patterns depending on their interactions with each other and with the ECM

Long-range mechanical force enables self-assembly of epithelial tubular patterns

Enabling long-range transport of molecules, tubules are critical for human body homeostasis. One fundamental question in tubule formation is how individual cells coordinate their positioning over long spatial scales, which can be as long as the sizes of tubular organs. Recent studies indicate that type I collagen (COL) is important in the development of epithelial tubules. Nevertheless, how cell–COL interactions contribute to the initiation or the maintenance of long-scale tubular patterns is unclear. Using a two-step process to quantitatively control cell–COL interaction, we show that epithelial cells developed various patterns in response to fine-tuned percentages of COL in ECM. In contrast with conventional thoughts, these patterns were initiated and maintained by traction forces created by cells but not diffusive factors secreted by cells. In particular, COL-dependent transmission of force in the ECM led to long-scale (up to 600 μm) interactions between cells. A mechanical feedback effect was encountered when cells used forces to modify cell positioning and COL distribution and orientations. Such feedback led to a bistability in the formation of linear, tubule-like patterns. Using micro-patterning technique, we further show that the stability of tubule-like patterns depended on the lengths of tubules. Our results suggest a mechanical mechanism that cells can use to initiate and maintain long-scale tubular patterns

Wide-field optical sectioning for live-tissue imaging by plane-projection multiphoton microscopy

Optical sectioning provides three-dimensional (3D) information in biological tissues. However, most imaging techniques implemented with optical sectioning are either slow or deleterious to live tissues. Here, we present a simple design for wide-field multiphoton microscopy, which provides optical sectioning at a reasonable frame rate and with a biocompatible laser dosage. The underlying mechanism of optical sectioning is diffuser-based temporal focusing. Axial resolution comparable to confocal microscopy is theoretically derived and experimentally demonstrated. To achieve a reasonable frame rate without increasing the laser power, a low-repetition-rate ultrafast laser amplifier was used in our setup. A frame rate comparable to that of epifluorescence microscopy was demonstrated in the 3D imaging of fluorescent protein expressed in live epithelial cell clusters. In this report, our design displays the potential to be widely used for video-rate live-tissue and embryo imaging with axial resolution comparable to laser scanning microscopy

Cell‐extracellular matrix interactions in the fluidic phase direct the topology and polarity of self‐organized epithelial structures

Introduction: In vivo, cells are surrounded by extracellular matrix (ECM). To build organs from single cells, it is generally believed that ECM serves as scaffolds to coordinate cell positioning and differentiation. Nevertheless, how cells utilize cell‐ECM interactions for the spatiotemporal coordination to different ECM at the tissue scale is not fully understood. Methods: Here, using in vitro assay with engineered MDCK cells expressing H2B‐mCherry (nucleus) and gp135/Podocalyxin‐GFP (apical marker), we show in multi‐dimensions that such coordination for epithelial morphogenesis can be determined by cell‐soluble ECM interaction in the fluidic phase. Results: The coordination depends on the native topology of ECM components such as sheet‐like basement membrane (BM) and type I collagen (COL) fibres: scaffold formed by BM (COL) facilitates a close‐ended (open‐ended) coordination that leads to the formation of lobular (tubular) epithelium. Further, cells form apicobasal polarity throughout the entire lobule/tubule without a complete coverage of ECM at the basal side, and time‐lapse two‐photon scanning imaging reveals the polarization occurring early and maintained through the lobular expansion. During polarization, gp135‐GFP was converged to the apical surface collectively in the lobular/tubular structures, suggesting possible intercellular communications. Under suspension culture, the polarization was impaired with multi‐lumen formation in the tubules, implying the importance of ECM biomechanical microenvironment. Conclusion: Our results suggest a biophysical mechanism for cells to form polarity and coordinate positioning at tissue scale, and in engineering epithelium through cell‐soluble ECM interaction and self‐assembly

A Computational Perspective on Network Coding

From the perspectives of graph theory and combinatorics theory we obtain some new upper bounds on the number of encoding nodes, which can characterize the coding complexity of the network coding, both in feasible acyclic and cyclic multicast networks. In contrast to previous work, during our analysis we first investigate the simple multicast network with source rate h=2, and then h≥2. We find that for feasible acyclic multicast networks our upper bound is exactly the lower bound given by M. Langberg et al. in 2006. So the gap between their lower and upper bounds for feasible acyclic multicast networks does not exist. Based on the new upper bound, we improve the computational complexity given by M. Langberg et al. in 2009. Moreover, these results further support the feasibility of signatures for network coding

Association between dynamic fluctuations in triiodothyronine levels and prognosis among critically ill patients within comprehensive intensive care units

ObjectiveDecrease in free thyroid hormone T3 (FT3) can be used as an independent prognostic indicator for the risk of death in ICUs. However, FT3 as a predictive marker is hindered by its accuracy. The study introduces the concept of dynamic FT3 data as a means to bolster the value of FT3 as a prognostic tool. Therefore, the aim of this study is to investigate the prognostic value of dynamic FT3 evolution in a comprehensive ICU setting, analyze the consistency between dynamic FT3 changes and variations in disease severity, and explore the feasibility of FT3 as an objective indicator for real-time clinical treatment feedback.MethodsEmploying a single-center prospective observational study, FT3 measurements were taken on multiple days following enrollment, corresponding clinical data were collected. To investigated the pattern of dynamic changes of FT3,its prognostic significance in forecasting the risk of 28-day mortality, the alignment between dynamic FT3 changes and variations in the Sequential Organ Failure Assessment (SOFA) score.ResultsThe survival group exhibited higher last FT3 levels compared to the lowest point (p<0.05), while the death group did not show statistically significant differences (p>0.05). The study also identifies the optimal correlation between FT3 and SOFA score at day 5 (optimal correlation coefficient -0.546).The ROC curve for FT3 at day 5 yielded an optimal AUC of 0.88, outperforming the SOFA score. The study categorizes FT3 curve patterns,Kaplan-Meier survival analysis of these patterns highlighted that the descending-type curve was significantly associated with increased risk of death (P<0.001). Additionally, the research explores the consistency between changes in FT3 and SOFA scores. While overall consistency rates were modest, subgroup analyses unveiled that greater disease severity led to higher consistency rates.ConclusionsThis study introduces the concept of dynamic FT3 changes to augment its prognostic utility in comprehensive ICU settings. The research identifies day 5 as the optimal time point for predictive efficacy, the descending FT3 curve as indicative of poor prognosis. While overall consistency with SOFA scores is modest, the correlation strengthens with greater disease severity

Polymeric pH nanosensor with extended measurement range bearing octaarginine as cell penetrating peptide

A synthetic peptide octaarginine which mimics human immunodeficiency virus‐1, Tat protein is used as cell penetrating moiety for new pH nanosensors which demonstrate enhanced cellular uptake and expanded measurement range from pH 3.9 to pH 7.3 by simultaneously incorporating two complemental pH‐sensitive fluorophores in a same nanoparticle. The authors believe that this triple fluorescent pH sensor provides a new tool to pH measurements that can have application in cellular uptake mechanism study and new nanomedicine design