Physical constraints on accuracy and persistence during breast cancer cell chemotaxis

Directed cell motion in response to an external chemical gradient occurs in many biological phenomena such as wound healing, angiogenesis, and cancer metastasis. Chemotaxis is often characterized by the accuracy, persistence, and speed of cell motion, but whether any of these quantities is physically constrained by the others is poorly understood. Using a combination of theory, simulations, and 3D chemotaxis assays on single metastatic breast cancer cells, we investigate the links among these different aspects of chemotactic performance. In particular, we observe in both experiments and simulations that the chemotactic accuracy, but not the persistence or speed, increases with the gradient strength. We use a random walk model to explain this result and to propose that cells' chemotactic accuracy and persistence are mutually constrained. Our results suggest that key aspects of chemotactic performance are inherently limited regardless of how favorable the environmental conditions are

Cell-matrix Interactions During En Masse Cell Migration

Extended wound care, including prolonged treatment of burn injuries, acute and chronic wounds, is a significant source of patient discomfort and financial burden to public healthcare programs. Both accelerated healing and prevention of scar formation are highly desired but remain to be challenging to achieve. This is primary due to limited understanding of interactions between cells and the surrounding extracellular matrix (ECM) during wound healing. Particularly, collective migration of fibroblasts through provisional matrix, so called en masse migration, is one of these interactions that play a critical role in later stages of granulation tissue formation and wound closure. In addition to biochemical cues, mechanical properties of the tissue are recently being considered to play a significant role during these processes. In particular, both stiffness of ECM is suggested as important factors for single cell migration. However, it is still not clear how these mechanical factors affect bi-directional interactions between a group of fibroblasts and the ECM. In order to address this question, we performed measurements of fibroblast migration on collagen matrices where matrix stiffness was independently varied by controlling collagen concentrations. (Expected results) It was found that the extent of fibroblast migration increased as stiffness of substrate increased. The results of this study are useful to understand the mechanical interactions between cells and ECM during wound healing and have implications to development of new wound dressings for improved wound healing outcomes

Tumor-microenvironment-on-chip to Mimic Tumor Heterogeneity

Ductal Carcinoma In Situ (DCIS) is a non-invasive cancer that forms around breast milk ducts that can potentially progress into invasive breast cancer if untreated. Lack of models to study its diverse pathophysiology and differential response to treatments poses a challenge to develop standard treatment modalities with improved therapeutic outcomes. The traditional in vitro models such as cell monolayer are convenient but insufficient to represent the physiological characteristics of DCIS tumor microenvironment and often fail to predict clinical outcomes. The animal models effectively simulate the in vivo environment but also lack the ability to control the environmental parameters to match specific conditions making it difficult to address the heterogeneities in disease state and patient-to-patient variations. It is critical to develop a new DCIS model system that offers physiologically relevant features with high degree of control. In order to address this need, a novel microfluidic in vitro model was developed. A lumen structure to represent the milk duct in breast was generated along the microfluidic channel using a fluid dynamic phenomenon called viscous finger patterning in which as the less viscous fluid passes through, it leaves a continuous trail that makes a hollow tubular structure in the collagen hydrogel. Consequently, MCF-7 breast cancer cell lines were cultured along the lumen surface with BR5 stromal fibroblast in collagen hydrogel. A relatively straight, smooth lumen was achieved at a higher concentration of collagen gel by viscous finger patterning with an optimal flow rate. The interaction between a non-invasive breast cancer cell line, MCF-7 and stromal fibroblast most likely remain unchanged, thus mimicking the DCIS. This new model system is a potential tool to study DCIS progression and treatment response by offering physiologically relevant features that can be tailored to match disease state and patient specific conditions

Investigation of Advanced Cathode Contacting Solutions in SOFC

Contacting solutions for air electrode in Solid Oxide Cells stacks often implement a ceramic paste made of electronic conducting perovskite, comparable or same as the electro-active material. This contacting layer, is applied in a green state by wet-powder-spray or screen-printing, and in situ fired during stack commissioning. The low level of necking between ceramic particles causes increased ohmic losses. Moreover the shrinkage usually observed during long term operation in temperature of this layer, due to sintering effect, lead to cracks and contact losses which hinder the cell performance. Increasing cell’s footprint, performance and lifetime at the stack level requires appropriate contacting solution. In this paper we reports the investigation of a new advanced monolithic contacting solution, easy to handle, soft and flexible, highly porous and highly conductive. Two different compositions have been investigated, with respect of their compatibility with Crofer (SEM, XRD). In addition, solid oxide cells contacted with this solution as well as with a ceramic paste have also been electrochemically tested up to 1000 hours in order to compare and assess the impact of this contacting solution on cell’s performance. Results will be presented and discussed

Recapitulation of complex transport and action of drugs at tumor microenvironment using tumor-microenvironment-on-chip

Targeted delivery aims to selectively distribute drugs to targeted tumor tissue but not to healthy tissue. This can address many of clinical challenges by maximizing the efficacy but minimizing the toxicity of anti-cancer drugs. However, complex tumor microenvironment poses various barriers hindering the transport of drugs and drug delivery systems. New tumor models that allow for the systematic study of these complex environments are highly desired to provide reliable test beds to develop drug delivery systems for targeted delivery. Recently, research efforts have yielded new in vitro tumor models, the so called tumor-microenvironment-on-chip, that recapitulate certain characteristics of the tumor microenvironment. These new models show benefits over other conventional tumor models, and have the potential to accelerate drug discovery and enable precision medicines. However, further research is warranted to overcome their limitations and to properly interpret the data obtained from these models. In this article, key features of the in vivo tumor microenvironment that are relevant to drug transport processes for targeted delivery was discussed, and the current status and challenges for developing in vitro transport model systems was reviewed

Matrix rigidity regulates spatiotemporal dynamics of Cdc42 activity and vacuole formation kinetics of endothelial colony forming cells

Recent evidence has shown that endothelial colony forming cells (ECFCs) may serve as a cell therapy for improving blood vessel formation in subjects with vascular injury, largely due to their robust vasculogenic potential. The Rho family GTPase Cdc42 is known to play a primary role in this vasculogenesis process, but little is known about how extracellular matrix (ECM) rigidity affects Cdc42 activity during the process. In this study, we addressed two questions: Does matrix rigidity affect Cdc42 activity in ECFC undergoing early vacuole formation? How is the spatiotemporal activation of Cdc42 related to ECFC vacuole formation? A fluorescence resonance energy transfer (FRET)-based Cdc42 biosensor was used to examine the effects of the rigidity of three-dimensional (3D) collagen matrices on spatiotemporal activity of Cdc42 in ECFCs. Collagen matrix stiffness was modulated by varying the collagen concentration and therefore fibril density. The results showed that soft (150 Pa) matrices induced an increased level of Cdc42 activity compared to stiff (1 kPa) matrices. Time-course imaging and colocalization analysis of Cdc42 activity and vacuole formation revealed that Cdc42 activity was colocalized to the periphery of cytoplasmic vacuoles. Moreover, soft matrices generated faster and larger vacuoles than stiff matrices. The matrix-driven vacuole formation was enhanced by a constitutively active Cdc42 mutant, but significantly inhibited by a dominant-negative Cdc42 mutant. Collectively, the results suggest that matrix rigidity is a strong regulator of Cdc42 activity and vacuole formation kinetics, and that enhanced activity of Cdc42 is an important step in early vacuole formation in ECFCs

Análisis y valoración del capital intelectual desarrollado por las maquiladoras del norte de Tamaulipas, México: el caso de Nuevo Laredo

Conocer la contribución que las Empresas extranjeras maquiladoras, ahora Industria Manufacturera, Maquiladora y de Servicios de Exportación (IMMEX) aportan a México. En la actualidad hay más de 5,000 empresas, generan 2´300,000 fuentes de trabajo directo, INEGI (2015). Aprovechando la integración económica y su situación geográfica del país continúan instalándose más. La IMMEX tiene su twin en el extranjero, por tal, un alto porcentaje de su producción se exporta. Son empresas globalizadas, favorecen así al país ingresando divisas. Para el caso de Nuevo Laredo, identificar el sector IMMEX que prodiga conocimiento, capacita y adiestramiento al personal, permitiendo así, conocer y manipular tecnología de última generación. La investigación y desarrollo propicia valor agregado, induce a innovar productos, las twins transfieren esa tecnología a su IMMEX. La competitiva y desarrollo se sustenta implantando procesos productivos y normas medio ambientales, ofreciendo seguridad dentro y fuera de la empresa, para identificase como Empresa Socialmente Responsable