http://bioinformatics.oxfordjournals.org – Interferon-β induced JAK-STAT signaling pathways contribute to mucosal immune recognition and an anti-viral state. Though the main molecular mechanisms constituting these pathways are known, neither the detailed structure of the regulatory network, nor its dynamics has yet been investigated. Read more »

http://www.springerlink.com – Changes in strain distribution across the vertebrate skeleton induce modelling and remodelling of bone structure. This relationship, like many in biomedical science, has been recognised since the 1800s, but it is only the recent development of in vivo and in vitro models that is allowing detailed investigation of the cellular mechanisms involved. A number of secondary messenger pathways have been implicated in load transduction by bone cells, and many of these pathways are similar to those proposed for other load-responsive cell types. Read more »

http://www.sciencedirect.com – Oncologists often diagnose cancer based on a change of tissue stiffness sensed by palpation, yet cancer researchers generally focus on biochemical signaling mechanisms. Tumors are more rigid because they have a stiffer extracellular matrix. A new study shows that this alteration of matrix mechanics activates integrins, which not only promotes mitogenic signaling through Erk but also cell contractility through Rho, which can further increase matrix stiffness. This establishes a positive feedback loop that switches on the malignant phenotype in mammary epithelial cells. Read more »

http://www.jbiomech.com – Mechnotransduction, the phenomenon by which cells respond to applied force, is necessary for normal cell processes and is implicated in the pathology of several diseases including atherosclerosis. The exact mechanisms which govern how forces can affect gene expression have not been determined, but putative direct force effects on the genome would require transduction through the nuclear lamina. In this study we show that nuclei in cells exposed to shear stress significantly change shape, upregulate nuclear lamins and move lamins from the nuclear interior to the nuclear periphery. Read more »

http://www.sciencedirect.com – There is a common mechanism for mechanotransduction in cells, regardless of the cell type. Integrins, interacting with their matrix/environment, mediate increases in intracellular Ca2+ levels and activate MAP kinase cascades to cause ERK1/2 phosphorylation. Phosphorylated ERK1/2 causes the activation of the AP-1 family of transcription factors that are necessary for the pro-growth response. The pro-bone growth response involves upregulation of the genes c-fos, IGF-1, cyclooxygenase, and osteocalcin. Read more »

http://circres.ahajournals.org – Great advances have been made in the identification of the soluble angiogenic factors, insoluble extracellular matrix (ECM) molecules, and receptor signaling pathways that mediate control of angiogenesis—the growth of blood capillaries. This review focuses on work that explores how endothelial cells integrate these chemical signals with mechanical cues from their local tissue microenvironment so as to produce functional capillary networks that exhibit specialized form as well as function. Read more »

http://www.sciencedirect.com – Microenvironments appear important in stem cell lineage specification but can be difficult to adequately characterize or control with soft tissues. Naive mesenchymal stem cells (MSCs) are shown here to specify lineage and commit to phenotypes with extreme sensitivity to tissue-level elasticity. Soft matrices that mimic brain are neurogenic, stiffer matrices that mimic muscle are myogenic, and comparatively rigid matrices that mimic collagenous bone prove osteogenic. Read more »

http://www.pnas.org – Physical forces generated by cells drive morphologic changes during development and can feedback to regulate cellular phenotypes. Because these phenomena typically occur within a 3-dimensional (3D) matrix in vivo, we used microelectromechanical systems (MEMS) technology to generate arrays of microtissues consisting of cells encapsulated within 3D micropatterned matrices. Microcantilevers were used to simultaneously constrain the remodeling of a collagen gel and to report forces generated during this process. By concurrently measuring forces and observing matrix remodeling Read more »

http://www.ncbi.nlm.nih.gov – Mechanosensitive pathways can be categorized as being amongst the oldest response pathways that developed in the history of evolution as they underlie many of the more complex physiological processes that developed later. Day to day examples that can be easily overlooked are the way organisms distinguish sound or respond to touch. This article deals with the mechanosensitive pathways of one particular example of worm, Caenorhabditis elegans. Read more »

http://cancerres.aacrjournals.org – Glioblastoma multiforme (GBM) is a malignant astrocytoma of the central nervous system associated with a median survival time of 15 months, even with aggressive therapy. This rapid progression is due in part to diffuse infiltration of single tumor cells into the brain parenchyma, which is thought to involve aberrant interactions between tumor cells and the extracellular matrix (ECM). Here, we test the hypothesis that mechanical cues from the ECM contribute to key tumor cell properties relevant to invasion. Read more »