Project description:Differentiated PC12 cells were magnetically labeled with magnetic nanoparticles (MNP). External magnetic fields were used to mechanically stretch the MNP-labeled neurites. We found that mechanical stretching of the neurites induces mass addition and neurite elongation. We performed RNAseq of MNP-labelled cells in stretched versus non-stretched conditions and we did not found gene expression dysregulation, confirming that the two conditions were identical and excluding cytotoxicity or involvement of nuclear mechanotransdution. Indeed, local mechanisms triggered by the stretching of the MNP-labelled neurite would be responsible for neurite elongation.
Project description:With gene expression profiling it was aimed to identify the differentially expressed genes associated with the regulation of the cytoskeleton to investigate the stretch-induced cell alignment mechanism. A whole genome microarray based analysis of the stretch-induced gene expression changes was done. Gene expression was measured at the beginning of the alignment process showing first reoriented cells after 5 h stretching and at the end after 24 h, where nearly all cells are aligned. Cyclic mechanical stretching of cells results in cellular alignment perpendicular to the stretch direction regulating cellular response. This stress response is assumed to be an adaptation mechanism to reduce extensive stretching but also acts as architectural restructuring changing performance and biomechanics of the tissue. Gene expression profiling of control vs. stretched primary human dermal fibroblasts after 5 h and 24 h demonstrated the regulation of differentially expressed genes associated with metabolism, differentiation and morphology.
Project description:The development of meter-long axons within the nervous system is a remarkable, yet unresolved biological process. The most widely studied aspects of neuronal growth focus on the extension and chemotropism of growth cones. However, over the course of organismal development, short axons elongate up to one meter in length with the systemic expansion of mitotic tissues. The preeminent regulatory mechanism for such synchronized growth between the nervous system and the tissues it spans, is the biomechanical stretch of axons, a known stimulus of axon growth. Here, we reveal the transcriptional profile of stretch-mediated axon growth as found using embryonic rat dorsal root ganglia neurons stretch-grown in vitro.
Project description:With gene expression profiling it was aimed to identify the differentially expressed genes associated with the regulation of the cytoskeleton to investigate the stretch-induced cell alignment mechanism. A whole genome microarray based analysis of the stretch-induced gene expression changes was done. Gene expression was measured at the beginning of the alignment process showing first reoriented cells after 5 h stretching and at the end after 24 h, where nearly all cells are aligned. Cyclic mechanical stretching of cells results in cellular alignment perpendicular to the stretch direction regulating cellular response. This stress response is assumed to be an adaptation mechanism to reduce extensive stretching but also acts as architectural restructuring changing performance and biomechanics of the tissue. Gene expression profiling of control vs. stretched primary human dermal fibroblasts after 5 h and 24 h demonstrated the regulation of differentially expressed genes associated with metabolism, differentiation and morphology. Primary human dermal fibroblasts from ten donors were cultured on Bioflex culture plates and stretched for 5h and 24 h or left untreated to avoid changes according to cell culturing. Each of the subject provided 4 samples (control/treated and 5hrs/24hrs) resulting in 40 samples total.
Project description:The goal of this study was to examine the effect of the major axis of biaxial mechanical stretch on cardiac myocyte gene expression and to identify the signaling pathways and transcription factors regulating these changes. Neonatal cardiac myocytes were cultured on a micropatterned substrate, and the primary stretch axis was applied either parallel or transverse to the myofibril direction. RNA sequencing was conducted to study whole genomic expression changes after acute cardiac myocyte stretch. The results showed a more robust gene response to longitudinal than to transverse stretch. After 30 minutes of stretch, 53 and 168 genes were considered differentially expressed (DE) from transverse and longitudinal stretch, respectively. After 4 hours, the number of DE genes increased to 795 in longitudinal stretch while it decreased to 35 in transverse stretch. Gene ontology term (GO) analysis indicated enrichment of TF activity and protein kinase activity by both stretch axes; whereas longitudinal but not transverse stretch caused expression of genes involved in sarcomere organization and cytoskeletal protein binding.
Project description:Analysis of gene expression patterns in enlarged left atrial appendage (LAA) in mitral/aortic valve replacement or coronary artery bypass graft surgery can help to identify a comprehensive panel of gene biomarkers for predicting clinical outcomes and to discover potential new therapeutic targets. However, the transcriptional profiles triggered by extended mechanical stretch in cardiac myocytes are not fully understood. Here we performed the first genome-wide study of gene expression changes in human enlarged left atium, resulting in 335 differentially expressed (> 2-fold, P < 0,05) genes in response to mechanical stretch.
Project description:Vascular smooth muscle cells (VSMCs) respond to biomechanical stretch with specific changes in gene expression which govern the phenotype of these cells. The mechanotransducer zyxin is a potential candidate for regulating the expression of such genes. Using microarrays, we compared stretch-induced gene expression in wild type and zyxin-null VSMCs to define such changes in detail.