Jain Gaurav, Ford Andrew J, Rajagopalan Padmavathy
School of Biomedical Engineering and Sciences, §Department of Chemical Engineering, and ⊥ICTAS Center for Systems Biology of Engineered Tissues, Virginia Tech, Blacksburg, Virginia 24061, United States.
School of Biomedical Engineering and Sciences, Department of Chemical Engineering, and ⊥ICTAS Center for Systems Biology of Engineered Tissues, Virginia Tech, Blacksburg, Virginia 24061, United States.
ACS Biomater Sci Eng. 2015 Aug 10;1(8):621-631. doi: 10.1021/acsbiomaterials.5b00229. Epub 2015 Jul 30.
The migration of cells is a complex and dynamic process that is governed by several stimuli acting simultaneously. In vivo, cells receive and process a wide range of cues that guide their motion and migratory characteristics such as speed and directionality. The design of biomaterials that can recapitulate the combinatorial signaling environment can aid in understanding how migrating cells respond to more than one stimulus and when one cue dominates over the other. We have designed hydrogel substrates that exhibit opposing rigidity-and collagen gradients. Within the boundaries of the interfacial region, the values for substrate modulus decreased in one direction with a concomitant increase in the concentration of surface-bound collagen. The well-known durotactic migration of fibroblasts was first validated on substrates that only exhibit a gradient in modulus while keeping the concentration of surface-bound collagen constant. Upon increasing the collagen concentration on the low-modulus regions by 4- or 7-fold compared to the high-modulus side of the interface, cells exhibited directed migration toward the soft regions of the substrate. This effect was more pronounced when the surface-bound collagen concentration was 7-fold greater. Cell displacements, areas, cytoskeleton and focal adhesions were investigated on the opposing rigidity-immobilized collagen gradients. These features were affected by the elastic modulus of the substrate as well as the change in protein concentration. In the future, incorporating multiple gradients within a single substrate will lead to a deeper and more comprehensive understanding of cells navigate through the complex in vivo microenvironment.
细胞迁移是一个复杂且动态的过程，受多种同时作用的刺激因素调控。在体内，细胞接收并处理各种线索，这些线索引导它们的运动以及迁移特性，如速度和方向性。能够重现组合信号环境的生物材料设计，有助于理解迁移细胞如何对多种刺激做出反应，以及何时一种线索比另一种更具主导性。我们设计了具有相反刚度和胶原蛋白梯度的水凝胶基质。在界面区域的边界内，基质模量的值在一个方向上降低，同时表面结合的胶原蛋白浓度增加。成纤维细胞众所周知的趋硬性迁移首先在仅表现出模量梯度而表面结合的胶原蛋白浓度保持恒定的基质上得到验证。与界面的高模量侧相比，当低模量区域的胶原蛋白浓度增加4倍或7倍时，细胞表现出向基质柔软区域的定向迁移。当表面结合的胶原蛋白浓度高7倍时，这种效应更为明显。在相反刚度固定的胶原蛋白梯度上研究了细胞位移、面积、细胞骨架和粘着斑。这些特征受基质的弹性模量以及蛋白质浓度变化的影响。未来，在单一基质中纳入多个梯度将有助于更深入、更全面地理解细胞如何在复杂的体内微环境中导航。
