Browsing by Subject "stretch"

Now showing 1 - 3 of 3
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    Effects of biomechanical forces on signaling in the cortical collecting duct (CCD)
    (American Physiological Society (APS), 2014-07-15) Carrisoza-Gaytan, Rolando; Liu, Yu; Flores, Daniel; Else, Cindy; Lee, Heon Goo; Rhodes, George; Sandoval, Ruben M.; Kleyman, Thomas R.; Lee, Francis Young-In; Molitoris, Bruce; Satlin, Lisa M.; Rohatgi, Rajeev; Department of Medicine, IU School of Medicine
    An increase in tubular fluid flow rate (TFF) stimulates Na reabsorption and K secretion in the cortical collecting duct (CCD) and subjects cells therein to biomechanical forces including fluid shear stress (FSS) and circumferential stretch (CS). Intracellular MAPK and extracellular autocrine/paracrine PGE2 signaling regulate cation transport in the CCD and, at least in other systems, are affected by biomechanical forces. We hypothesized that FSS and CS differentially affect MAPK signaling and PGE2 release to modulate cation transport in the CCD. To validate that CS is a physiological force in vivo, we applied the intravital microscopic approach to rodent kidneys in vivo to show that saline or furosemide injection led to a 46.5 ± 2.0 or 170 ± 32% increase, respectively, in distal tubular diameter. Next, murine CCD (mpkCCD) cells were grown on glass or silicone coated with collagen type IV and subjected to 0 or 0.4 dyne/cm2 of FSS or 10% CS, respectively, forces chosen based on prior biomechanical modeling of ex vivo microperfused CCDs. Cells exposed to FSS expressed an approximately twofold greater abundance of phospho(p)-ERK and p-p38 vs. static cells, while CS did not alter p-p38 and p-ERK expression compared with unstretched controls. FSS induced whereas CS reduced PGE2 release by ∼40%. In conclusion, FSS and CS differentially affect ERK and p38 activation and PGE2 release in a cell culture model of the CD. We speculate that TFF differentially regulates biomechanical signaling and, in turn, cation transport in the CCD.
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    Mechano-sensitivity of nuclear lamin proteins in endothelial cells
    (2016-07-22) Jiang, Yizhi; Ji, Julie Ying Hui; Na, Sungsoo; Wallace, Joseph
    Atherosclerosis is a chronic disease that happens mostly in aged people, and recently studies have showed many similarities between Hutchinson Gilford Progeria Syndrome (HGPS) cells and aging cells, implicating dysfunctions of lamin A/C in aging process and atherosclerosis, as HGPS is caused by a mutated form of lamin A/C. Blood flow in arteries is generating shear stress that is mostly applied on endothelial cells that align along inner blood vessel wall. At the same time, endothelial cells are also under stretch by periodic arterial pulses. Considering the fact that atherosclerosis is prone to developing at arterial branches with disturbed shear and increased stretch, it is highly possible that laminar flow and proper stretch force are regulating endothelium to function appropriately. In this thesis, the investigation of what effects laminar flow or cyclic stretch can bring to endothelial cells was conducted, and examination of lamin A/C expression under mechanical forces were elaborated and incorporated with cell senescence. Results showed that laminar shear stress and stretch force can regulate lamin A/C expression in different patterns, which were impaired in senescent cells.
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    A novel in vitro stretch device for simulating in vivo conditions
    (2018-05) Akella, Arun; El-Mounayri, Hazim
    Biological cells are constantly subjected to mechanical forces such as tension, compression and shear. The importance of these forces in mediating cell signals, maintenance of lineages, promoting embryonic cell differentiation and tissue engineering is only now coming into focus. It has been shown that stretch stimulus can influence growth, differentiation, as well as tissue strength and integrity. Most stretch systems built to understand more of these phenomena suffer from shortcomings, as accurately replicating the in vivo environment is quite challenging. Many of the devices currently available are very expensive as well as limited to a single application. The objective of this thesis is to design, manufacture, test, and validate a novel uniaxial cyclic cell stretch device that overcomes most of the major limitations of existing systems, and to experimentally demostrate that uniaxial cyclic stretch causes a shift towards in vivo characteristics of smooth muscle cells. The stretch mechanism is driven by a single servo motor which makes its operation simple and straight forward. Coolworks Lite, a proprietary software of the servo motor supplier, is used to control the motor and LabVIEW is used to obtain feedback from the sensors. Validation for the stretch machine was done by evaluating the performance of the device against engineering requirements. Methods were suggested to improve shortcomings that were encountered. Also, the machine's unique design allows its extension to a biaxial stretch unit while keeping the same driver platform, a concept for which has been discussed and illustrated.