Emerging Roles of YAP/TAZ in Mechanobiology

Sun, Yubing; Shao, Yue; Xue, Xufeng; Fu, Jianping

doi:10.1007/978-1-4939-5617-3_4

Cited by 1 publication

(2 citation statements)

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“…Cell spread area can also regulate subcellular localization of YAP, with small cell spread area promoting YAP cytoplasmic localization [20, 23, 33]. Thus, we further examined whether ATC stimulation could promote nuclear localization of YAP in patterned single hMSCs with defined cell areas of different sizes (30 × 30 μm 2 and 100 × 100 μm 2 ).…”

Section: Resultsmentioning

confidence: 99%

“…Importantly, RhoA/ROCK-mediated cytoskeletal contractility is critically involved in mechanotransduction in hMSCs [16–19]. Recent studies also indicate the importance of YAP signaling in controlling mechanosensitive hMSC osteogenesis, highlighting mechanotransductive mechanisms acting upstream of YAP transcriptional activity through Rho GTPases, cytoskeletal contractility, and F-actin mechanics [8, 9, 20–24]. Altogether, mechanosensitive hMSC osteogenesis has been suggested to be regulated through RhoA/ROCK/myosin-II signaling axis and the mechanosensitive transcriptional regulator YAP; however, the functional link between the RhoA/ROCK/myosin-II signaling axis and YAP activity in hMSCs remains to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

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Acoustic tweezing cytometry enhances osteogenesis of human mesenchymal stem cells through cytoskeletal contractility and YAP activation

Xue

Hong

et al. 2017

Biomaterials

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Human mesenchymal stem cells (hMSCs) have great potential for cell-based therapies for treating degenerative bone diseases. It is known that mechanical cues in the cell microenvironment play an important role in regulating osteogenic (bone) differentiation of hMSCs. However, mechanoregulation of lineage commitment of hMSCs in conventional two-dimensional (2D) monocultures or bioengineered three-dimensional (3D) tissue constructs remains suboptimal due to complex biomaterial design criteria for hMSC culture. In this study, we demonstrate the feasibility of a novel cell mechanics and mechanobiology tool, acoustic tweezing cytometry (ATC), for mechanical stimulation of hMSCs. ATC utilizes ultrasound (US) pulses to actuate functionalized lipid microbubbles (MBs) which are covalently attached to hMSCs via integrin binding to exert forces to the cells. ATC stimulation increases cytoskeletal contractility of hMSCs regardless of the cell area. Furthermore, ATC application rescues osteogenic differentiation of hMSCs in culture conditions that are intrinsically repressive for hMSC osteogenesis (e.g., soft cell culture surfaces). ATC application activates transcriptional regulator YAP to enhance hMSC osteogenesis. Our data further show that F-actin, myosin II, and RhoA/ROCK signaling function upstream of YAP activity in mediating ATC-stimulated hMSC osteogenesis. With the capability of applying controlled dynamic mechanical stimuli to cells, ATC provides a powerful tool for mechanoregulation of stem cell behaviors in tissue engineering and regenerative medicine applications.

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Section: Resultsmentioning

confidence: 99%