Center for Bioengineering and Tissue Regeneration, Department of Surgery, University of California San Francisco, San Francisco, CA, USA.
UC Berkeley-UCSF Graduate Program in Bioengineering, San Francisco, CA, USA.
Philos Trans R Soc Lond B Biol Sci. 2019 Aug 19;374(1779):20180215. doi: 10.1098/rstb.2018.0215. Epub 2019 Jul 1.
A growing body of work describes how physical forces in and around cells affect their growth, proliferation, migration, function and differentiation into specialized types. How cells receive and respond biochemically to mechanical signals is a process termed mechanotransduction. Disease may arise if a disruption occurs within this mechanism of sensing and interpreting mechanics. Cancer, cardiovascular diseases and developmental defects, such as during the process of neural tube formation, are linked to changes in cell and tissue mechanics. A breakdown in normal tissue and cellular forces activates mechanosignalling pathways that affect their function and can promote disease progression. The recent advent of high-resolution techniques enables quantitative measurements of mechanical properties of the cell and its extracellular matrix, providing insight into how mechanotransduction is regulated. In this review, we will address the standard methods and new technologies available to properly measure mechanical properties, highlighting the challenges and limitations of probing different length-scales. We will focus on the unique environment present throughout the development and maintenance of the central nervous system and discuss cases where disease, such as brain cancer, arises in response to changes in the mechanical properties of the microenvironment that disrupt homeostasis. This article is part of a discussion meeting issue 'Forces in cancer: interdisciplinary approaches in tumour mechanobiology'.
越来越多的研究描述了细胞内外的物理力如何影响细胞的生长、增殖、迁移、功能以及分化为特定类型。细胞如何接收和生化响应机械信号是一个被称为机械转导的过程。如果这个感知和解释力学的机制发生了中断,就可能会引发疾病。癌症、心血管疾病和发育缺陷,如神经管形成过程中的缺陷,都与细胞和组织力学的变化有关。正常组织和细胞力的崩溃会激活机械信号通路,影响它们的功能,并促进疾病的进展。最近出现的高分辨率技术能够定量测量细胞及其细胞外基质的力学特性,深入了解机械转导是如何被调节的。在这篇综述中,我们将介绍可用于正确测量力学特性的标准方法和新技术,重点讨论探测不同长度尺度所面临的挑战和局限性。我们将重点关注贯穿中枢神经系统发育和维持过程中存在的独特环境,并讨论在某些情况下,如脑癌,疾病是如何因微环境力学特性的变化而发生的,这些变化破坏了体内平衡。本文是关于“癌症中的力:肿瘤机械生物学的跨学科方法”讨论专题的一部分。