PDF(Pubmed)
Abstract：
Controlling cell-substrate interactions via the microstructural characteristics of biomaterials offers an advantageous path for modulating cell dynamics, mechanosensing, and migration, as well as for designing immune-modulating implants, all without the drawbacks of chemical-based triggers. Specifically, recent in vivo studies have suggested that a porous implant\'s microscale curvature landscape can significantly impact cell behavior and ultimately the immune response. To investigate such cell-substrate interactions, we utilized a 3D computational model incorporating the minimum necessary physics of cell migration and cell-substrate interactions needed to replicate known in vitro behaviors. This model specifically incorporates the effect of membrane tension, which was found to be necessary to replicate in vitro cell behavior on curved surfaces. Our simulated substrates represent two classes of porous materials recently used in implant studies, which have markedly different microscale curvature distributions and pore geometries. We found distinct differences between the overall migration behaviors, shapes, and actin polymerization dynamics of cells interacting with the two substrates. These differences were correlated to the shape energy of the cells as they interacted with the porous substrates, in effect interpreting substrate topography as an energetic landscape interrogated by cells. Our results demonstrate that microscale curvature directly influences cell shape and migration and, therefore, is likely to influence cell behavior. This supports further investigation of the relationship between the surface topography of implanted materials and the characteristic immune response, a complete understanding of which would broadly advance principles of biomaterial design.
摘要：
通过生物材料的微观结构特征控制细胞-基质相互作用为调节细胞动力学提供了有利的途径。机械传感,和移民,以及设计免疫调节植入物，所有这些都没有基于化学的触发器的缺点。具体来说,最近的体内研究表明，多孔植入物的微尺度曲率景观可以显著影响细胞行为和最终的免疫反应。为了研究这种细胞-底物相互作用，我们使用了3D计算模型,该模型结合了复制已知体外行为所需的细胞迁移和细胞-基质相互作用的最低必要物理条件.该模型特别结合了膜张力的影响，发现这对于在曲面上复制体外细胞行为是必需的。我们的模拟基材代表了最近用于植入物研究的两类多孔材料，具有明显不同的微观曲率分布和孔隙几何形状。我们发现总体迁移行为之间存在明显差异，形状,以及与两种底物相互作用的细胞的肌动蛋白聚合动力学。这些差异与细胞与多孔基质相互作用时的形状能量相关，实际上将基底地形解释为细胞询问的充满活力的景观。我们的结果表明，微尺度曲率直接影响细胞形状和迁移，因此,可能会影响细胞行为。这支持进一步研究植入材料的表面形貌与特征性免疫反应之间的关系。对其的完整理解将广泛推进生物材料设计的原则。
