Engineered Fibrillar Microenvironments With Controllable Architecture and Mechanics for Studying Cellular Stiffness Sensing
Engineered Fibrillar Microenvironments With Controllable Architecture and Mechanics for Studying Cellular Stiffness Sensing
复制标题
具有可控结构和力学的工程纤维微环境用于研究细胞刚度传感
DOI：
10.1115/sbc2013-14804
复制
发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Christopher S. Chen
中科院分区：
文献类型：
--
作者：
Brendon M. Baker;B. Trappmann;Iris L. Kim;J. Burdick;Christopher S. Chen
细胞外基质(ECM)的力学特性已经成为许多基本细胞功能的基本参与者，如扩散、迁移、增殖和分化，从而影响许多生物过程，包括胚胎发育、成人组织动态平衡以及疾病发病机制，如纤维化和癌症[1，2，3]。合成基质对于研究力学对细胞行为的影响至关重要，因为它们允许在很大的硬度范围内精确控制力学性能，这在体内或许多自然衍生材料系统中是无法实现的。使用不同硬度的聚丙烯酰胺水凝胶指导人骨髓间充质干细胞分化的开创性工作得出结论：体积弹性系数是衡量材料对均匀变形的抵抗力的指标，是影响细胞功能的决定性参数[4]。虽然目前的许多努力都旨在阐明刚度感知的分子机制，但现有的知识受到这些研究中使用的简单水凝胶表面与体内常规存在的更复杂的细胞外基质细胞的不同之处的限制。与细胞黏附配体的平展和典型凝胶系统的线弹性、连续体行为不同，在体内，细胞尺度的力学和配体的可用性是交织在一起的，因为两者都由组成周围细胞外基质的蛋白质的存在和组织来定义。天然细胞外基质的结构各不相同，但大部分是纤维状的，因为胶原蛋白约占人体质量的25%。因此，对工程纤维材料的需求仍然很大，这种材料能够精确和独立地控制细胞生物学中的结构特征和由此产生的机械性能。在这项工作中，我们建立了一个新的材料体系来实现这一目标。版权所有©2013 by ASME
The mechanical properties of the extracellular matrix (ECM) have emerged as fundamental players in numerous basic cellular functions such as spreading, migration, proliferation and differentiation, thus impacting many biological processes including embryonic development, adult tissue homeostasis, and disease pathogenesis such as fibrosis and cancer [1,2,3]. Synthetic matrices have been crucial to studying the effect of mechanics on cell behavior, as they allow for precise control of mechanical properties over a wide stiffness range, unachievable in vivo or in many naturally derived material systems. Seminal work employing polyacrylamide hydrogels of varying stiffness to direct the differentiation of human mesenchymal stem cells concluded that the bulk modulus, a measure of the material’s resistance to uniform deformation, is a defining parameter influencing cell function [4]. While much current effort aims to shed light on the molecular mechanisms governing stiffness sensing, existing knowledge is limited by the dissimilarity between the simple hydrogel surfaces employed in these studies and the topographically and mechanically more complex ECM cells routinely reside within in vivo. In contrast to the flat expanse of cell adhesive ligand and linear elastic, continuum behavior of typical gel systems, within the body, cell-scale mechanics and ligand availability are entwined, as both are defined by the presence and organization of the proteins that compose the surrounding ECM. The structure of native ECMs vary but largely are fibrillar, given that collagen comprises approximately 25% of the human body by mass. Thus, there remains a significant need for engineered fibrillar materials that afford precise and independent control of architectural features and resulting mechanical properties for application in cell biology. In this work, we establish a novel material system towards this end.Copyright © 2013 by ASME