Biophysical Engineering Lab, University of Pennsylvania, Philadelphia, PA 19104, USA.
J Cell Sci. 2010 Feb 1;123(Pt 3):297-308. doi: 10.1242/jcs.041186.
Cellular organization within a multicellular organism requires that a cell assess its relative location, taking in multiple cues from its microenvironment. Given that the extracellular matrix (ECM) consists of the most abundant proteins in animals and contributes both structure and elasticity to tissues, ECM probably provides key physical cues to cells. In vivo, in the vicinity of many tissue cell types, fibrous characteristics of the ECM are less discernible than the measurably distinct elasticity that characterizes different tissue microenvironments. As a cell engages matrix and actively probes, it senses the local elastic resistance of the ECM and nearby cells via their deformation, and--similar to the proverbial princess who feels a pea placed many mattresses below--the cell seems to possess feedback and recognition mechanisms that establish how far it can feel. Recent experimental findings and computational modeling of cell and matrix mechanics lend insight into the subcellular range of sensitivity. Continuity of deformation from the matrix into the cell and further into the cytoskeleton-caged and -linked nucleus also supports the existence of mechanisms that direct processes such as gene expression in the differentiation of stem cells. Ultimately, cells feel the difference between stiff or soft and thick or thin surroundings, regardless of whether or not they are of royal descent.
多细胞生物中的细胞组织需要细胞评估其相对位置,从微环境中获取多种线索。鉴于细胞外基质(ECM)由动物中最丰富的蛋白质组成,并为组织提供结构和弹性,因此 ECM 可能为细胞提供关键的物理线索。在体内,在许多组织细胞类型的附近,ECM 的纤维特征不如可测量的不同组织微环境的弹性特征明显。当细胞与基质接触并主动探测时,它会通过其变形来感知 ECM 和附近细胞的局部弹性阻力,就像寓言中的公主感觉到放在许多床垫下面的豌豆一样,细胞似乎具有反馈和识别机制,可以确定它能感觉到多远。细胞和基质力学的最新实验发现和计算模型为亚细胞灵敏度范围提供了深入了解。从基质到细胞再到细胞骨架笼状和连接核的变形连续性也支持存在这样的机制,这些机制可以指导干细胞分化过程中的基因表达等过程。最终,无论它们是否出身王室,细胞都会感受到坚硬或柔软、厚实或稀薄环境之间的差异。