Smooth muscle cell phenotype modulation and contraction on native and cross-linked polyelectrolyte multilayers.

Smooth muscle cell phenotype modulation and contraction on native and cross-linked polyelectrolyte multilayers.
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DOI:
10.1021/bm9007309
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发表时间:
2009-11-09
期刊:
影响因子:
6.2
通讯作者:
Schlenoff, Joseph B.
Schlenoff, Joseph B.
中科院分区:
化学2区
文献类型:
--
作者:
Moussallem, Maroun D.;Olenych, Scott G.;Scott, Shannon L.;Keller, Thomas C. S., III;Schlenoff, Joseph B.

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平滑肌细胞在运动的、增殖的“合成”表型和固着的、“收缩”表型之间转换。研究了具有共同表面化学特性但刚度不同的薄生物相容性多层膜(PEMU)操纵主动脉平滑肌细胞表型的能力。通过加热以在层之间形成共价酰胺键交联来改变(PAH/PAA)PEMU的刚度。原子力显微镜(AFM)显示,交联PEMU比那些没有交联薄。原子力显微镜纳米压痕表明,杨氏模量范围从6 MPa的水合原生PEMU超过8 GPa的最大交联PEMU。大鼠主动脉A7 r5平滑肌细胞培养的天然PEMU表现出合成细胞的形态和运动性和合成表型标志物波形蛋白,原肌球蛋白4,和非肌肉肌球蛋白重链IIB(nmMHCIIB)的表达。相比之下,在最大交联PEMU上培养的细胞表现出表型标志物钙调蛋白、平滑肌肌球蛋白重链(smMHC)、肌心蛋白、transgelin和平滑肌α-肌动蛋白(smActin),这些标志物是平滑肌“收缩”表型的特征。与那些细胞是“收缩性的”一致,当用Ca 2+离子载体刺激时,在交联PEMU上生长的A7 r5细胞产生收缩力。
Smooth muscle cells convert between a motile, proliferative “synthetic” phenotype and a sessile, “contractile” phenotype. The ability to manipulate the phenotype of aortic smooth muscle cells with thin biocompatible polyelectrolyte multilayers (PEMUs) with common surface chemical characteristics but varying stiffness was investigated. The stiffness of (PAH/PAA) PEMUs was varied by heating to form covalent amide bond cross-links between the layers. Atomic force microscopy (AFM) showed that cross-linked PEMUs were thinner than those that were not cross-linked. AFM nanoindentation demonstrated that the Young’s modulus ranged from 6 MPa for hydrated native PEMUs to more than 8 GPa for maximally cross-linked PEMUs. Rat aortic A7r5 smooth muscle cells cultured on native PEMUs exhibited morphology and motility of synthetic cells and expression of the synthetic phenotype markers vimentin, tropomyosin 4, and nonmuscle myosin heavy chain IIB (nmMHCIIB). In comparison, cells cultured on maximally cross-linked PEMUs exhibited the phenotype markers calponin, smooth muscle myosin heavy chain (smMHC), myocardin, transgelin, and smooth muscle α-actin (smActin) that are characteristic of the smooth muscle “contractile” phenotype. Consistent with those cells being “contractile”, A7r5 cells grown on cross-linked PEMUs produced contractile force when stimulated with a Ca2+ ionophore.
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