Spatiotemporal control of cardiac anisotropy using dynamic nanotopographic cues.
Spatiotemporal control of cardiac anisotropy using dynamic nanotopographic cues.
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DOI：
10.1016/j.biomaterials.2016.01.062
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发表时间：
2016-04
期刊：
影响因子：
14
通讯作者：
Kim DH
中科院分区：
文献类型：
--
作者：
Mengsteab PY;Uto K;Smith AS;Frankel S;Fisher E;Nawas Z;Macadangdang J;Ebara M;Kim DH
协调的细胞外基质时空重组有助于调节体内细胞分化、成熟和功能，因此对于复杂解剖结构的正确形成、维持和愈合至关重要。为了评估培养的细胞响应其体外微环境中的动态变化的潜力，正如它们在体内所做的那样，研究了在具有可控各向异性形貌的纳米制造基底上培养的原代心肌细胞的集体行为。采用热致形状记忆聚合物（SMP）评估基底图案取向的90°转变对心肌细胞片的收缩方向和结构组织的影响。培养在SMPs上的心肌细胞片在形状转变前表现出各向异性收缩。在热诱导形状转变后48小时，心肌细胞收缩的方向显著重新定向，并呈现双峰分布，峰值在~ 45度和-45度（P < 0.001）。免疫细胞化学分析强调了细胞在响应底层地形变化时发生的显著结构变化。所呈现的结果表明，初始各向异性纳米地形线索并不能永久决定培养中心肌细胞的组织命运或收缩特性。考虑到表面线索在调节原代细胞和干细胞发育中的重要性，对这种可调纳米形貌的研究可能对促进细胞体外成熟和性能以及提高我们对动态生物物理线索响应的细胞发育的理解具有重要意义。
Coordinated extracellular matrix spatiotemporal reorganization helps regulate cellular differentiation, maturation, and function in vivo, and is therefore vital for the correct formation, maintenance, and healing of complex anatomic structures. In order to evaluate the potential for cultured cells to respond to dynamic changes in their in vitro microenvironment, as they do in vivo, the collective behavior of primary cardiac muscle cells cultured on nanofabricated substrates with controllable anisotropic topographies was studied. A thermally induced shape memory polymer (SMP) was employed to assess the effects of a 90° transition in substrate pattern orientation on the contractile direction and structural organization of cardiomyocyte sheets. Cardiomyocyte sheets cultured on SMPs exhibited anisotropic contractions before shape transition. 48 hours after heat-induced shape transition, the direction of cardiomyocyte contraction reoriented significantly and exhibited a bimodal distribution, with peaks at ~ 45 and −45 degrees (P < 0.001). Immunocytochemical analysis highlighted the significant structural changes that the cells underwent in response to the shift in underlying topography. The presented results demonstrate that initial anisotropic nanotopographic cues do not permanently determine the organizational fate or contractile properties of cardiomyocytes in culture. Given the importance of surface cues in regulating primary and stem cell development, investigation of such tunable nanotopographies may have important implications for advancing cellular maturation and performance in vitro, as well as improving our understanding of cellular development in response to dynamic biophysical cues.