期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2016
卷号：113
期号：49
页码：14043-14048
DOI：10.1073/pnas.1613058113
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceMechanical interactions between cells and the ECM critically regulate cell function, including growth and migration. By measuring forces exerted by breast tumor cells embedded within collagen matrices, we reveal a positive mechanical cross-talk between the cell and ECM: cells pulling onto collagen fibers align and stiffen the matrices, and stiffer collagen matrices promote greater cell force generation. Our work highlights the importance of strain-induced fiber alignment in mediating cell-ECM interaction within a 3D architecture. The basic force regulation principle uncovered here can be extended to understand the tissue-stiffening processes occurring in many diseases, such as tumor progression and fibrosis, and better design biomaterial scaffolds to control cell behavior in tissue engineering applications. In native states, animal cells of many types are supported by a fibrous network that forms the main structural component of the ECM. Mechanical interactions between cells and the 3D ECM critically regulate cell function, including growth and migration. However, the physical mechanism that governs the cell interaction with fibrous 3D ECM is still not known. In this article, we present single-cell traction force measurements using breast tumor cells embedded within 3D collagen matrices. We recreate the breast tumor mechanical environment by controlling the microstructure and density of type I collagen matrices. Our results reveal a positive mechanical feedback loop: cells pulling on collagen locally align and stiffen the matrix, and stiffer matrices, in return, promote greater cell force generation and a stiffer cell body. Furthermore, cell force transmission distance increases with the degree of strain-induced fiber alignment and stiffening of the collagen matrices. These findings highlight the importance of the nonlinear elasticity of fibrous matrices in regulating cell-ECM interactions within a 3D context, and the cell force regulation principle that we uncover may contribute to the rapid mechanical tissue stiffening occurring in many diseases, including cancer and fibrosis.
关键词：cell traction force ; 3D cell traction force microscopy ; fibrous nonlinear elasticity ; cell–ECM interaction ; collagen
