Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
Biomaterials. 2012 Jun;33(16):4126-35. doi: 10.1016/j.biomaterials.2012.02.047. Epub 2012 Mar 13.
In vivo, vascular endothelial cells (VECs) are anchored to the underlying stroma through a specialization of the extracellular matrix, the basement membrane (BM) which provides a variety of substratum associated biophysical cues that have been shown to regulate fundamental VEC behaviors. VEC function and homeostasis are also influenced by hemodynamic cues applied to their apical surface. How the combination of these biophysical cues impacts fundamental VEC behavior remains poorly studied. In the present study, we investigated the impact of providing biophysical cues simultaneously to the basal and apical surfaces of human aortic endothelial cells (HAECs). Anisotropically ordered patterned surfaces of alternating ridges and grooves and isotropic holed surfaces of varying pitch (pitch = ridge or hole width + intervening groove or planar regions) were fabricated and seeded with HAECs. The cells were then subjected to a steady shear stress of 20 dyne/cm(2) applied either parallel or perpendicular to the direction of the ridge/groove topography. HAECs subjected to flow parallel to the ridge/groove topography exhibited protagonistic effects of the two stimuli on cellular orientation and elongation. In contrast, flow perpendicular to the substrate topography resulted in largely antagonistic effects. Interestingly, the behavior depended on the shape and size of the topographic features. HAECs exhibited a response that was less influenced by the substratum and primarily driven by flow on isotropically ordered holed surfaces of identical pitch to the anistropically ordered surfaces of alternating ridges and grooves. Simultaneous presentation of biophysical cues to the basal and apical aspects of cells also influenced nuclear orientation and elongation; however, the extent of nuclear realignment was more modest in comparison to cellular realignment regardless of the surface order of topographic features. Flow-induced HAEC migration was also influenced by the ridge/groove surface topographic features with significantly altered migration direction and increased migration tortuosity when flow was oriented perpendicular to the topography; this effect was also pitch-dependent. The present findings provide valuable insight into the interaction of biologically relevant apical and basal biophysical cues in regulating cellular behavior and promise to inform improved prosthetic design.
在体内，血管内皮细胞（VEC）通过细胞外基质的特化，即基底膜（BM），与基底膜相连，基底膜为细胞提供了各种与基质相关的生物物理线索，这些线索已被证明可以调节基本的 VEC 行为。VEC 的功能和动态平衡也受到施加在其顶端表面的血液动力学线索的影响。这些生物物理线索的组合如何影响基本的 VEC 行为仍研究甚少。在本研究中，我们研究了同时向人主动脉内皮细胞（HAEC）的基底和顶端表面提供生物物理线索的影响。交替脊和槽的各向异性有序图案表面和各向同性孔表面（孔间距=脊或孔的宽度+中间槽或平面区域）被制造并接种 HAEC。然后，将细胞施加 20 达因/厘米 2 的稳态剪切应力，该剪切应力平行或垂直于脊/槽形貌的方向施加。HAEC 受到平行于脊/槽形貌的流动作用时，细胞的定向和伸长表现出两种刺激的主导作用。相比之下，垂直于基底形貌的流动导致的作用则主要是拮抗的。有趣的是，该行为取决于形貌特征的形状和大小。HAEC 在各向同性有序的孔表面上表现出对基底和顶端的响应，该表面的形状和大小与各向异性有序的交替脊和槽的表面相同，对流动的影响较小。同时向细胞的基底和顶端方面呈现生物物理线索也会影响核的定向和伸长；然而，无论形貌特征的表面顺序如何，核的重新排列程度都比细胞的重新排列程度要小。流动诱导的 HAEC 迁移也受到脊/槽表面形貌特征的影响，当流动方向垂直于形貌时，迁移方向发生明显改变，迁移扭曲度增加；这种效应也依赖于孔间距。本研究结果为调节细胞行为的生物相关顶端和基底生物物理线索的相互作用提供了有价值的见解，并有望为改进的假体设计提供信息。
