Department of Biomedical Engineering, University of Minnesota, Nils Hasselmo Hall, Room 7-105 312 Church Street SE, Minneapolis, MN 55455.
J Biomech Eng. 2021 Oct 1;143(10). doi: 10.1115/1.4051117.
Arteries grow and remodel following mechanical perturbation. Vascular smooth muscle cells (VSMCs) within the artery undergo hyperplasia, hypertrophy, or change their contractility following sustained changes in loading. Experimental evidence in vivo and in vitro suggests that VSMCs grow and remodel to maintain a constant transmural stress, or "target" stress. This behavior is often described using a stress-dependent finite growth framework. Typically, computational models of arterial growth and remodeling account for VSMC behavior in a constrained mixture formulation that incorporates behavior of each component of the artery. However, these models do not account for differential VSMC architecture observed in situ, which may significantly influence growth and remodeling behavior. Here, we used cellular microbiaxial stretching (CμBS) to characterize how VSMCs with different cytoskeletal architectures respond to a sustained step change in strain. We find that VSMC F-actin architecture becomes more aligned following stretch and retains this alignment after 24 h. Further, we find that VSMC stress magnitude depends on cellular architecture. Qualitatively, however, stress behavior following stretch is consistent across cell architectures-stress increases following stretch and returns to prestretch magnitudes after 24 h. Finally, we formulated an architecture-dependent targeted growth law that accounts for experimentally measured cytoskeletal alignment and attributes stress evolution to individual fiber growth and find that this model robustly captures long-term stress evolution in single VSMCs. These results suggest that VSMC mechano-adaptation depends on cellular architecture, which has implications for growth and remodeling in regions of arteries with differential architecture, such as at bifurcations.
动脉会在受到机械干扰后生长和重塑。血管平滑肌细胞（VSMC）在动脉中会发生增生、肥大或改变其收缩性，这是在持续的负载变化下发生的。体内和体外的实验证据表明，VSMC 会生长和重塑，以维持恒定的壁间应力，或“目标”应力。这种行为通常使用依赖于应力的有限生长框架来描述。通常，动脉生长和重塑的计算模型考虑了 VSMC 在约束混合物公式中的行为，其中包含了动脉各组成部分的行为。然而，这些模型没有考虑到原位观察到的 VSMC 结构的差异，这可能会显著影响生长和重塑行为。在这里，我们使用细胞微双轴拉伸（CμBS）来描述具有不同细胞骨架结构的 VSMC 如何对应变的持续阶跃变化做出反应。我们发现，VSMC 的 F-肌动蛋白结构在拉伸后变得更加对齐，并在 24 小时后保持这种对齐。此外，我们发现 VSMC 的应力大小取决于细胞结构。然而，在拉伸后，应力行为在质上是一致的，无论是在细胞结构之间——拉伸后应力增加，并在 24 小时后恢复到拉伸前的大小。最后，我们提出了一个依赖于结构的靶向生长定律，该定律考虑了实验测量的细胞骨架对齐，并将应力演化归因于单个纤维的生长，我们发现该模型能够很好地捕捉单个 VSMC 中的长期应力演化。这些结果表明，VSMC 的机械适应性取决于细胞结构，这对具有不同结构的动脉区域（如分叉处）的生长和重塑有影响。
