Use of optical tweezers to probe epithelial mechanosensation

Resnick, Andrew

doi:10.1117/1.3316378

Cited by 20 publications

(15 citation statements)

References 46 publications

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“…Controlled extension of silicone [10] or hydrogel [11] substrates can mimic ECM stretching in vivo. More targeted methods of physically perturbing cells include the use of optical tweezers [12], atomic force microscopy [13], and magnetic twisting cytometry [14]. Some of these tools have also been used to assess “inside-out” mechanosensing by measuring the force with which a cell pulls on its extracellular environment [15].…”

Section: Controlling the Physical Microenvironment Of The Cellmentioning

confidence: 99%

More than a feeling: discovering, understanding, and influencing mechanosensing pathways

Holle

Engler

2011

Current Opinion in Biotechnology

129

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Section: Controlling the Physical Microenvironment Of The Cellmentioning

confidence: 99%

More than a feeling: discovering, understanding, and influencing mechanosensing pathways

Holle

Engler

2011

Current Opinion in Biotechnology

129

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“…129 Third, Using laser tweezers, Resnick et al . 128 applied mechanical forces directly to the apical surface of MDCK cells and found a null intracellular Ca 2+ response indicating that the apical membrane does not participate in mechanotransduction. Collectively, these results strongly suggest that primary cilia are the mechanosensing organelle in the CCD.…”

Section: In Vivo In Situ and Cell Culture Experiments To Validate Thmentioning

confidence: 99%

An Integrative Review of Mechanotransduction in Endothelial, Epithelial (Renal) and Dendritic Cells (Osteocytes)

et al. 2011

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In this review we will examine from a biomechanical and ultrastructural viewpoint how the cytoskeletal specialization of three basic cell types, endothelial cells (ECs), epithelial cells (renal tubule) and dendritic cells (osteocytes), enables the mechano-sensing of fluid flow in both their native in vivo environment and in culture, and the downstream signaling that is initiated at the molecular level in response to fluid flow. These cellular responses will be discussed in terms of basic mysteries and paradoxes encountered by each cell type. In ECs fluid shear stress (FSS) is nearly entirely attenuated by the endothelial glycocalyx that covers their apical membrane and yet FSS is communicated to both intracellular and junctional molecular components in activating a wide variety of signaling pathways. The same is true in proximal tubule (PT) cells where a dense brush border of microvilli covers the apical surface and the flow at the apical membrane is negligible. A four decade old unexplained mystery is the ability of PT epithelia to reliably reabsorb 60% of the flow entering the tubule regardless of the glomerular filtration rate. In the cortical collecting duct (CCD) the flow rates are so low that a special sensing apparatus, a primary cilia is needed to detect very small variations in tubular flow. In bone it has been a century old mystery as to how osteocytes embedded in a stiff mineralized tissue are able to sense miniscule whole tissue strains that are far smaller than the cellular level strains required to activate osteocytes in vitro.

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“…Long considered vestigial structures, recent work has conclusively demonstrated that the primary cilium is in fact a calcium signaling center for the cell [1] organizing a large number of signaling pathways. Demonstrations that bending a primary cilium via fluid flow [2], optical tweezers [3], or micropipette [4] initiates intracellular calcium release imply that physiologically, the primary cilium is a flow sensor. However, the biological significance of this function remains unclear.…”

Section: Introductionmentioning

confidence: 99%

HIF Stabilization Weakens Primary Cilia

Resnick

2016

PLoS ONE

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Although solitary or sensory cilia are present in most cells of the body and their existence has been known since the sixties, very little is known about their functions. One suspected function is fluid flow sensing- physical bending of cilia produces an influx of Ca++, which can then result in a variety of activated signaling pathways. Defective cilia and ciliary-associated proteins have been shown to result in cystic diseases. Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a progressive disease, typically appearing in the 5th decade of life and is one of the most common monogenetic inherited human diseases, affecting approximately 600,000 people in the United States. Because the mechanical properties of cilia impact their response to applied flow, we asked how the stiffness of cilia can be controlled pharmacologically. We performed an experiment subjecting cilia to Taxol (a microtubule stabilizer) and CoCl2 (a HIF stabilizer to model hypoxia). Madin-Darby Canine Kidney (MDCK) cells were selected as our model system. After incubation with a selected pharmacological agent, cilia were optically trapped and the bending modulus measured. We found that HIF stabilization significantly weakens cilia. These results illustrate a method to alter the mechanical properties of primary cilia and potentially alter the flow sensing properties of cilia.

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Use of optical tweezers to probe epithelial mechanosensation

Cited by 20 publications

References 46 publications

More than a feeling: discovering, understanding, and influencing mechanosensing pathways

More than a feeling: discovering, understanding, and influencing mechanosensing pathways

An Integrative Review of Mechanotransduction in Endothelial, Epithelial (Renal) and Dendritic Cells (Osteocytes)

HIF Stabilization Weakens Primary Cilia

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