The contractile strength of vascular smooth muscle myocytes is shape dependent

Ye, George J.C.; Aratyn-Schaus, Yvonne; Nesmith, Alexander P.; Pasqualini, Francesco S.; Alford, Patrick W.; Parker, Kevin Kit

doi:10.1039/c3ib40230d

Cited by 37 publications

(47 citation statements)

References 81 publications

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“…2A). Quantification of actin alignment using a previously developed technique 14a revealed alignment to be statistically higher (p<0.05) at an AR of 1:7 compared to 1:5 and 1:3 (Fig. 2C).…”

Section: Resultsmentioning

confidence: 94%

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Valve interstitial cell contractile strength and metabolic state are dependent on its shape

et al. 2016

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The role of valvular interstitial cell (VIC) architecture in regulating cardiac valve function and pathology is not well understood. VICs are known to be more elongated in a hypertensive environment compared to those in a normotensive environment. We have previously reported that valve tissues cultured under hypertensive conditions are prone to acute pathological alterations in cell phenotype and contractility. We therefore aimed to rigorously study the relationship between VIC shape, contractile output and other functional indicators of VIC pathology. We developed an in vitro model to engineer VICs to take on the same shapes as those seen in normal and hypertensive conditions. VICs with longer cellular and nuclear shapes, as seen in hypertensive conditions, had greater contractile response to endothelin-1 that correlated with increased anisotropy of the actin architecture. These elongated VICs also demonstrated altered cell metabolism through a decreased optical redox ratio, which coincided with increased cellular proliferation. In the presence of actin polymerization inhibitor, however, these functional responses were significantly reduced, suggesting the important role of cytoskeletal actin organization in regulating cellular responses to abnormal shape. Overall, these results demonstrate the relationship between cell shape, cytoskeletal and nuclear organization, with functional output including contractility, metabolism, and proliferation.

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“…2A). Quantification of actin alignment using a previously developed technique 14a revealed alignment to be statistically higher (p<0.05) at an AR of 1:7 compared to 1:5 and 1:3 (Fig. 2C).…”

Section: Resultsmentioning

confidence: 94%

“…14 We therefore evaluated whether altered VIC shape resulted in changes in cytoskeletal and nuclear architecture. Phalloidin staining of F-actin, showed that the filaments became more prominent and aligned along the longitudinal direction of the cell as AR increased (Fig.…”

Section: Resultsmentioning

confidence: 99%

Valve interstitial cell contractile strength and metabolic state are dependent on its shape

et al. 2016

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“…The functionality of iSMC was also evaluated by traction force microscopy 35,36 . We compared the traction forces produced in control EPC and iSMC (4 weeks).…”

Section: Resultsmentioning

confidence: 99%

Transdifferentiation of human endothelial progenitors into smooth muscle cells

Atchison

Chen

et al. 2016

Biomaterials

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Access to smooth muscle cells (SMC) would create opportunities for tissue engineering, drug testing, and disease modeling. Herein we report the direct conversion of human endothelial progenitor cells (EPC) to induced smooth muscle cells (iSMC) by induced expression of MYOCD. The EPC undergo a cytoskeletal rearrangement resembling that of mesenchymal cells within 3 days post initiation of MYOCD expression. By day 7, the reprogrammed cells show upregulation of smooth muscle markers ACTA2, MYH11, and TAGLN by qRT-PCR and ACTA2 and MYH11 expression by immunofluorescence. By two weeks, they resemble umbilical artery SMC in microarray gene expression analysis. The iSMC, in contrast to EPC control, show calcium transients in response to phenylephrine stimulation and a contractility an order of magnitude higher than that of EPC as determined by traction force microscopy. Tissue-engineered blood vessels constructed using iSMC show functionality with respect to flow- and drug-mediated vasodilation and vasoconstriction.

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“…Cell elongation influences the behavior of many cell types, particularly myocytes, which rely on their shape for directional force generation. 18-20 While the function of macrophages in the body is quite different, these cells have been shown to exhibit different shapes in vivo, where M2 polarized cells are more elongated and often found within fibrous tissue architectures. 21-23 Immune cells may in fact share similar mechanisms with other cell types for sensing their extracellular environment.…”

Section: Introductionmentioning

confidence: 99%

Micro- and Nanopatterned Topographical Cues for Regulating Macrophage Cell Shape and Phenotype

Luu

Gott

Woo

et al. 2015

ACS Appl. Mater. Interfaces

280

201

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Controlling the interactions between macrophages and biomaterials is critical for modulating the response to implants. While it has long been thought that biomaterial surface chemistry regulates the immune response, recent studies have suggested that material geometry may in fact dominate. Our previous work demonstrated that elongation of macrophages regulates their polarization towards a pro-healing phenotype. In this work, we elucidate how surface topology might be leveraged to alter macrophage cell morphology and polarization state. Using a deep etch technique, we fabricated titanium surfaces containing micro and nano-patterned grooves, which have been previously shown to promote cell elongation. Morphology, phenotypic markers, and cytokine secretion of murine bone marrow derived macrophages on different groove widths were analyzed. The results suggest that micro and nano-patterned grooves influenced macrophage elongation, which peaked on substrates with 400-500 nm wide grooves. Surface grooves did not affect inflammatory activation, but drove macrophages towards an anti-inflammatory, pro-healing phenotype. While secretion of TNF-alpha remained low in macrophages across all conditions, macrophages secreted significantly higher levels of anti-inflammatory cytokine, IL-10, on intermediate groove widths compared to cells on other Ti surfaces. Our findings highlight the potential of using surface topography to regulate macrophage function, and thus control the wound healing and tissue repair response to biomaterials.

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The contractile strength of vascular smooth muscle myocytes is shape dependent

Cited by 37 publications

References 81 publications

Valve interstitial cell contractile strength and metabolic state are dependent on its shape

Valve interstitial cell contractile strength and metabolic state are dependent on its shape

Transdifferentiation of human endothelial progenitors into smooth muscle cells

Micro- and Nanopatterned Topographical Cues for Regulating Macrophage Cell Shape and Phenotype

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