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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 19 records

Gene regulation by mechanical forces

Endothelial cells are subjected to various mechanical forces in vivo from the flow of blood across the luminal surface of the blood vessel. The purpose of this review was to examine the data available on how these mechanical forces, in particular cyclic strain, affect the expression and regulation of endothelial cell function. Studies from various investigators using models of cyclic strain in vitro have shown that various vasoactive mediators such as nitric oxide and prostacyclin are induced by the effect of mechanical deformation, and that the expression of these mediators may be regulated at the transcription level by mechanical forces. There also seems to be emerging evidence that endothelial cells may also act as mechanotransducers, whereby the transmission of external forces induces various cytoskeletal changes and second messenger cascades. Furthermore, it seems these forces may act on specific response elements of promoter genes.

Review, Tutorial↗

Mechanical forces and their second messengers in stimulating cell growth in vitro

Mechanical forces play an important role in modulating the growth of a number of different tissues including skeletal muscle, smooth muscle, cardiac muscle, bone, endothelium, epithelium, and lung. As interest increases in the molecular mechanisms by which mechanical forces are transduced into growth alterations, model systems are being developed to study these processes in tissue culture. This paper reviews the current methods available for mechanically stimulating tissue cultured cells. It then outlines some of the putative 'mechanogenic' second messengers involved in altering cell growth. Not surprisingly, many mechanogenic second messengers are the same as those involved in growth factor-induced cell growth. It is hypothesized that from an evolutionary standpoint, some second messenger systems may have initially evolved for unicellular organisms to respond to physical forces such as gravity and mechanical perturbation in their environment. As multicellular organisms came into existence, they appropriated these mechanogenic second messenger cascades for cellular regulation by growth factors.

Vandenburgh, Herman H.↗

Solar Variability in the Context of Other Climate Forcing Mechanisms

I compare and contrast climate forcings due to solar variability with climate forcings due to other mechanisms of climate change, interpretation of the role of the sun in climate change depends upon climate sensitivity and upon the net forcing by other climate change mechanisms. Among the potential indirect climate forcings due to solar variability, only that due to solar cycle induced ozone changes has been well quantified. There is evidence that the sun has been a significant player in past climate change on decadal to century time scales, and that it has the potential to contribute to climate change in the 21st century.

Hansen, James E.↗

A short pulse of mechanical force induces gene expression and growth in MC3T3-E1 osteoblasts via an ERK 1/2 pathway

Physiological mechanical loading is crucial for maintenance of bone integrity and architecture. We have calculated the strain caused by gravity stress on osteoblasts and found that 4-30g corresponds to physiological levels of 40-300 microstrain. Short-term gravity loading (15 minutes) induced a 15-fold increase in expression of growth-related immediate early gene c-fos, a 5-fold increase in egr-1, and a 3-fold increase in autocrine bFGF. The non-growth-related genes EP-1, TGF-beta, and 18s were unaffected by gravity loading. Short-term physiological loading induced extracellular signal-regulated kinase (ERK 1/2) phosphorylation in a dose-dependent manner with maximum phosphorylation saturating at mechanical loading levels of 12g (p < 0.001) with no effect on total ERK. The phosphorylation of focal adhesion kinase (FAK) was unaffected by mechanical force. g-Loading did not activate P38 MAPK or c-jun N-terminal kinase (JNK). Additionally, a gravity pulse resulted in the localization of phosphorylated ERK 1/2 to the nucleus; this did not occur in unloaded cells. The induction of c-fos was inhibited 74% by the MEK1/2 inhibitor U0126 (p < 0.001) but was not affected by MEK1 or p38 MAPK-specific inhibitors. The long-term consequence of a single 15-minute gravity pulse was a 64% increase in cell growth (p < 0.001). U0126 significantly inhibited gravity-induced growth by 50% (p < 0.001). These studies suggest that short periods of physiological mechanical stress induce immediate early gene expression and growth in MC3T3-E1 osteoblasts primarily through an ERK 1/2-mediated pathway.

NASA Discipline Cell Biology↗

Analyzing Seasonal Forcing Mechanisms of the Martian Polar Warming with the NASA Ames Mars Global Climate Model

The meridional transport of heat, momentum, water, dust, trace species and gases is critical for the control of Mars’ climate. Though the nature and structure of the mean meridional circulation has been previously studied, questions remain regarding the seasonal forcing mechanisms, and the implications on the combined thermal and dynamical response for Mars’ climate. A useful diagnostic of the mean meridional circulation and transport in the middle atmosphere is polar warming.

Brecht, A. S.↗

Altering the cellular mechanical force balance results in integrated changes in cell, cytoskeletal and nuclear shape

Studies were carried out with capillary endothelial cells cultured on fibronectin (FN)-coated dishes in order to analyze the mechanism of cell and nuclear shape control by extracellular matrix (ECM). To examine the role of the cytoskeleton in shape determination independent of changes in transmembrane osmotic pressure, membranes of adherent cells were permeabilized with saponin (25 micrograms/ml) using a buffer that maintains the functional integrity of contractile microfilaments. Real-time videomicroscopic studies revealed that addition of 250 microM ATP resulted in time-dependent retraction and rounding of permeabilized cells and nuclei in a manner similar to that observed in intact living cells following detachment using trypsin-EDTA. Computerized image analysis confirmed that permeabilized cells remained essentially rigid in the absence of ATP and that retraction was stimulated in a dose-dependent manner as the concentration of ATP was raised from 10 to 250 microM. Maximal rounding occurred by 30 min with projected cell and nuclear areas being reduced by 69 and 41%, respectively. ATP-induced rounding was also accompanied by a redistribution of microfilaments resulting in formation of a dense net of F-actin surrounding retracted nuclei. Importantly, ATP-stimulated changes in cell, cytoskeletal, and nuclear form were prevented in permeabilized cells using a synthetic myosin peptide (IRICRKG) that has been previously shown to inhibit actomyosin filament sliding in muscle. In contrast, both the rate and extent of cell and nuclear rounding were increased in permeabilized cells exposed to ATP when the soluble FN peptide, GRGDSP, was used to dislodge immobilized FN from cell surface integrin receptors.(ABSTRACT TRUNCATED AT 250 WORDS).

Non-NASA Center↗

Disentangling the Roles of Various Forcing Mechanisms on Stratospheric Temperature Changes Since 1979 with the NASA GEOSCCM

Observations show that the cooling of global stratospheric temperatures from 1979 to 2015 took place in two major steps coincident with the 1982 El Chichon and 1991 Mount Pinatubo eruptions. In order to attribute the features of the global stratospheric temperature time series to the main forcing agents, we performed a set of simulations with the NASA Goddard Earth Observing System Chemistry Climate Model. Our results show that the characteristic step-like behavior is to be attributed to the effects of the solar cycle, except for the post-1995 flattening of the lower stratospheric temperatures, where the decrease in ozone depleting substances due to the Montreal Protocol slowed ozone depletion and therefore also the cooling of the stratosphere. Volcanic eruptions also caused a significant warming of the stratosphere after 1995. The observed general cooling is mainly caused by increasing ozone depleting substances in the lower stratosphere, and greenhouse gases in the middle and upper stratosphere.

ozone↗

Mechanical forces in plant growth and development

Plant cells perceive forces that arise from the environment and from the biophysics of plant growth. These forces provide meaningful cues that can affect the development of the plant. Seedlings of Arabidopsis thaliana were used to examine the cytoplasmic tensile character of cells that have been implicated in the gravitropic response. Laser-trapping technology revealed that the starch-containing statoliths of the central columella cells in root caps are held loosely within the cytoplasm. In contrast, the peripheral cells have starch granules that are relatively resistant to movement. The role of the actin cytoskeleton in affecting the tensile character of these cells is discussed. To explore the role that biophysical forces might play in generating developmental cues, we have developed an experimental model system in which protoplasts, embedded in a synthetic agarose matrix, are subjected to stretching or compression. We have found that protoplasts subjected to these forces from five minutes to two hours will subsequently elongate either at right angles or parallel to the tensive or compressive force vector. Moreover, the cortical microtubules are found to be organized either at right angles or parallel to the tensive or compressive force vector. We discuss these results in terms of an interplay of information between the extracellular matrix and the underlying cytoskeleton.

Non-NASA Center↗

Quasi-geostrophic free mode models of long-lived Jovian eddies: Forcing mechanisms and crucial observational tests

Observations of Jupiter and Saturn long-lived eddies, such as Jupiter's Great Red Spot and White Ovals, are presently compared with laboratory experiments and corresponding numerical simulations for free thermal convection in a rotating fluid that is subject to horizontal differential heating and cooling. Difficulties in determining the essential processes maintaining and dissipating stable eddies, on the basis of global energy budget studies, are discussed; such difficulties do not arise in considerations of the flow's potential vorticity budget. On Jupiter, diabatically forced and transient eddy-driven flows primarily differ in the implied role of transient eddies in transporting potential vorticity across closed geostrophic streamlines in the time mean.

Read, P. L.↗

A Study of Parameters Affecting Fibroblast Morphology in Response to an Applied Mechanical Force

A precisely controlled stretch/relaxation regimen (20% elongation at 6.6 cycles/min) was applied to normal human fetal, neonatal and aged dermal fibroblasts cultured on flexible membranes. Culture conditions included poly (NH2) or collagen type I coated substrate membranes; control cultures were grown on the same pliable material in the absence of applied stretch. Direct observation and immunofluorescence analyses revealed a progressive change in cell body orientation limited to the stretched dermal fibroblast cultures. Monolayers gradually (over 4 days) acquired a symmetric, radial distribution equivalent to the biaxial array of the applied force. At high seeding density, alignment was inhibited in the fetal cell cultures. This cell strain required collagen type I coating for optimal attachment to the flexible membrane, preferring growth in three-dimensional cell 'balls' on the poly(NH2) coated substrate. Neonatal cells also required the collagen type I coating, but both neonatal and aged dermal fibroblasts aligned efficiently at all seeding densities examined. The randomly oriented neonatal cells on the unstretched control membranes spontaneously detached at confluence, as a single cell sheet. Their aligned counterparts did not detach until the applied stretch stimulus was removed. Low concentrations of cytochalasin D (62.5 ng/ml) disrupted the stretch-related alignment response. Rhodamine phalloidin staining visualized fewer actin stress fibers in stretched, aligned cells than in controls. Both intercellular interactions and cytoskeletal integrity mediate the response to mechanical strain. Normal rabbit corneal stroma fibroblasts (NRC) were also analyzed, and failed to orient under these conditions. This cell type may require a different regimen, or a longer time period, to demonstrate alignment behavior. Supported by NASA Space Biology RTOP 199-40-22 and the NASA-ARC Director's Discretionary Fund.

Grymes, Rosalind A.↗

Investigation of mesoscale pre-convective forcing mechanisms

The installation and testing of a numerical mesoscale boundary layer model is discussed. A data analysis is first made using the rawinsonde network which shows a strong baroclinic zone developing in the region where convection was initiated. The observed wind field shows an easterly component developing in opposition to the synoptic flow producing convergence. The numerical boundary layer model is used to diagnose the physical development of the thermal and flow fields. Two physical mechanisms are examined; topography and cloud shading. The results shows that while heated sloping topography alone does create a baroclinic zone and convergence values, cloud shading is a stronger mechanism for producing a thermal field representative of observed conditions

Mcnider, R. T.↗

Sea ice concentrations in the Canada Basin during 1988 - Comparisons with other years and evidence of multiple forcing mechanisms

Results from a study of special sensor microwave imager data and visible band DMSP-OLS imagery show a large area of reduced ice concentration in the Canada Basin during summer 1988. Drifting buoys, surface pressure fields, output from the Polar Ice Prediction System sea ice model, and other meteorological data used to examine processes responsible for development of the reduced ice concentrations are discussed. It is noted that, while ice divergence in the summer offers a partial explanation, the model indicates that there are other factors which play contributing roles. Among these factors are the anomalously warm atmospheric conditions, generally clear skies in June and July, extensive fracturing of the pack ice in spring and anomalous advection of oceanic heat. It is found that the second and third of these effects may occur in most years. It is concluded that, although the extent and magnitude of the concentration reductions during 1988 are unusual, these recurring factors tend to predispose the pack ice in the Canada Basin to decay.

Serreze, Mark C.↗

Musculoskeletal adaptation to mechanical forces on Earth and in space

A major concern of the US and Russian space programs is the health and safety of astronauts and cosmonauts. One of the areas receiving the most attention has been the effects of long duration space flight on the musculoskeletel system. After three decades of space flight and research, questions continue. Can exercise in space maintain musculoskeletal tissue mass and function in an adult? The objective of this paper is to address this question in a way that hopefully provides a rational basis for quantifying and evaluating the influnence of daily activities on muscle and bone on Earth and in space.

Whalen, Robert↗

Mechanotransduction in bone: osteoblasts are more responsive to fluid forces than mechanical strain

Mechanical force applied to bone produces two localized mechanical signals on the cell: deformation of the extracellular matrix (substrate strain) and extracellular fluid flow. To study the effects of these stimuli on osteoblasts, MC3T3-E1 cells were grown on type I collagen-coated plastic plates and subjected to four-point bending. This technique produces uniform levels of physiological strain and fluid forces on the cells. Each of these parameters can be varied independently. Osteopontin (OPN) mRNA expression was used to assess the anabolic response of MC3T3-E1 cells. When fluid forces were low, neither strain magnitude nor strain rate was correlated with OPN expression. However, higher-magnitude fluid forces significantly increased OPN message levels independently of the strain magnitude or rate. These data indicate that fluid forces, and not mechanical stretch, influence OPN expression in osteoblasts and suggest that fluid forces induced by extracellular fluid flow within the bone matrix may play an important role in bone formation in response to mechanical loading.

Non-NASA Center↗

Hypergravity Loading the Cultured Osteoblasts: Modeling and Experimental Analysis of Cellular Morphology and the Cytoskeleton

Bone forming cells, osteoblasts, respond to various mechanical forces, including mechanical strain and fluid-induced shear stress. This study examined whether osteoblasts detect changes in gravity as a mechanical force, as assessed by cellular morphology and dimensions of the cytoskeletal network. We used modeling to evaluate how gravity influences cell morphology given theoretical differences in densities between the surrounding medium, cytoplasm, and nucleus. A mechanical model was built based on analysis of axisymmetric shell structures (Fast4 software) to study the effects of 10 times gravity (10G) on cell height. The model indicated 0.02% decrease in overall cell height when the medium was 10% denser than the nucleus or cytoplasm, 5.9 x 10(exp-5)% decrease when the nucleus was 10% denser than the cytoplasm or medium, and 1.3 x 10(exp-5)% decrease when the cell cytoplasm was 10% denser than the nucleus or medium. To experimentally evaluate the influence of gravity, cultured primary fetal rat osteoblasts were grown to near confluence and centrifuged at 10G for 3 hours. Actin, microtubules, and nuclei were fluorescently labeled and analyzed by confocal microscopy to determine overall microtubule and actin network height. Centrifugation led to an apparent reduction in height of both the microtubule (-16%) and the actin (-20%) networks relative to stationary controls. Thus, both modeling and experiments indicate that hypergravity reduces the height of the osteoblast cell layer and their microtubule and actin networks. This combination of modeling and experimental analyses will help us to better understand the mechanical loading of osteoblasts.

Searby, N. D.↗

The Cytoskeleton and Force Response Mechanisms

The long term aim of this project was to define the mechanisms by which cells sense and respond to the physical forces experienced at 1g and missing in microgravity. Identification and characterization of the elements of the cells force response mechanism could provide pathways and molecules to serve as targets for pharmacological intervention to mitigate the pathologic effects of microgravity. Mechanical forces experienced by the organism can be transmitted to cells through molecules that allow cells to bind to the extracellular matrix and through other types of molecules which bind cells to each other. These molecules are coupled in large complexes of proteins to structural elements such as the actin cytoskeleton that give the cell the ability to sense, resist and respond to force. Application of small forces to tissue culture cells causes local elevation of intracellular calcium through stretch activated ion channels, increased tyrosine phosphorylation and a restructuring of the actin cytoskeleton. Using collagen coated iron oxide beads and strong magnets, we can apply different levels of force to cells in culture. We have found that force application causes the cells to polymerize actin at the site of mechanical deformation and unexpectedly, to depolymerize actin across the rest of the cell. Observations of GFP- actin expressing cells demonstrate that actin accumulates at the site of deformation within the first five minutes of force application and is maintained for many tens of minutes after force is removed. Consistent with the reinforcement of the cytoskeletal structures underlying the integrin-bead interaction, force also alters the motion of bound magnetic beads. This effect is seen following the removal of the magnetic field, and is only partially ablated by actin disruption with cytochalsin B. While actin is polymerizing locally at the site of force application, force also stimulates a global reduction in actin filament content within the cells. We have examined the roles of several actin filament disassembly factors in the global reduction of cellular actin filaments. The calcium regulated actin filament severing protein gelsolin is not necessary for the increased actin turnover, as cells derived from gelsolin null and wildtype mice still show a reduction in total actin filament content. Instead, our work suggests that the actin binding protein cofilin may be important for these changes in actin dynamics. Cofilin binds to and enhances the disassembly of actin filaments. Using immunological methods, we observe transient changes in the phosphorylation state of cofilin upon force application that suggests that cofilin may mediate actin filament turnover. Early after force application, cofilin is transiently dephosphorylated, activating its actin disassembly activity. Subsequently, we find a hyper-phosphorylation of cofilin, rendering it inactive. This reduction in cofilin activity may explain the stability of the force induced actin structuttes. In testing this hypothesis, we aimed to generate cells that express the constituitively active kinase (LIM-kinase) that phosphorylates cofilin. lnidial attempts in the cell lines used for the our previous studies proved unsuccessful. While we prepare this work for pubication, we are continuing to study other cell lines and tissue sources to determine whether they show a reduction in F-actin content after force application.

Allen, Philip Goodwin↗

Cellular control lies in the balance of forces

Mechanical tension generated within the cytoskeleton of living cells is emerging as a critical regulator of biological function in diverse situations ranging from the control of chromosome movement to the morphogenesis of the vertebrate brain. In this article, we review recent advances that have been made in terms of understanding how cells generate, transmit and sense mechanical tension, as well as how they use these forces to control their shape and behavior. An integrated view of cell regulation that incorporates mechanics and structure as well as chemistry is beginning to emerge.

Review, Tutorial↗