Wyss Institute for Biologically Inspired Engineering, Harvard University, and Department of Pathology, Children's Hospital, Boston, MA 02115-5737, USA.
Ann Biomed Eng. 2010 Mar;38(3):1148-61. doi: 10.1007/s10439-010-9946-0.
This article is based on a lecture I presented as the recipient of the 2009 Pritzker Distinguished Lecturer Award at the Biomedical Engineering Society annual meeting in October 2009. Here, I review more than thirty years of research from my laboratory, beginning with studies designed to test the theory that cells use tensegrity (tensional integrity) architecture to stabilize their shape and sense mechanical signals, which I believed to be critical for control of cell function and tissue development. Although I was trained as a cell biologist, I found that the tools I had at my disposal were insufficient to experimentally test these theories, and thus I ventured into engineering to find critical solutions. This path has been extremely fruitful as it has led to confirmation of the critical role that physical forces play in developmental control, as well as how cells sense and respond to mechanical signals at the molecular level through a process known as cellular mechanotransduction. Many of the predictions of the cellular tensegrity model relating to cell mechanical behaviors have been shown to be valid, and this vision of cell structure led to discovery of the central role that transmembrane adhesion receptors, such as integrins, and the cytoskeleton play in mechanosensing and mechanochemical conversion. In addition, these fundamental studies have led to significant unexpected technology fallout, including development of micromagnetic actuators for non-invasive control of cellular signaling, microfluidic systems as therapeutic extracorporeal devices for sepsis therapy, and new DNA-based nanobiotechnology approaches that permit construction of artificial tensegrities that mimic properties of living materials for applications in tissue engineering and regenerative medicine.
这篇文章是基于我在 2009 年 10 月举行的生物医学工程学会年会上作为 2009 年普利兹克杰出讲师奖获得者发表的演讲。在这里，我回顾了我实验室三十多年的研究工作，从旨在检验细胞利用张拉整体（张力完整性）结构来稳定其形状和感知机械信号的理论的研究开始，我认为这对于控制细胞功能和组织发育至关重要。尽管我是一名细胞生物学家，但我发现我所掌握的工具不足以通过实验来检验这些理论，因此我冒险进入工程领域寻找关键解决方案。这条道路是非常富有成效的，因为它证实了物理力在发育控制中起着关键作用，以及细胞如何在分子水平上通过称为细胞机械转导的过程感知和响应机械信号。与细胞机械行为相关的细胞张拉整体模型的许多预测已被证明是有效的，这种细胞结构的观点导致发现了跨膜粘附受体（如整合素）和细胞骨架在机械传感和机械化学转换中的核心作用。此外，这些基础研究还带来了重大的意外技术成果，包括开发用于非侵入性控制细胞信号的微磁致动器、用于败血症治疗的体外治疗微流控系统，以及新的基于 DNA 的纳米生物技术方法，这些方法允许构建模仿生物材料特性的人工张拉整体，用于组织工程和再生医学应用。
