Suresh Subra
Department of Materials Science and Engineering, Division of Biological Engineering, and Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139-4307, USA.
Acta Biomater. 2007 Jul;3(4):413-38. doi: 10.1016/j.actbio.2007.04.002. Epub 2007 May 30.
The past decade has seen substantial growth in research into how changes in the biomechanical and biophysical properties of cells and subcellular structures influence, and are influenced by, the onset and progression of human diseases. This paper presents an overview of the rapidly expanding, nascent field of research that deals with the biomechanics and biophysics of cancer cells. The review begins with some key observations on the biology of cancer cells and on the role of actin microfilaments, intermediate filaments and microtubule biopolymer cytoskeletal components in influencing cell mechanics, locomotion, differentiation and neoplastic transformation. In order to set the scene for mechanistic discussions of the connections among alterations to subcellular structures, attendant changes in cell deformability, cytoadherence, migration, invasion and tumor metastasis, a survey is presented of the various quantitative mechanical and physical assays to extract the elastic and viscoelastic deformability of cancer cells. Results available in the literature on cell mechanics for different types of cancer are then reviewed. Representative case studies are presented next to illustrate how chemically induced cytoskeletal changes, biomechanical responses and signals from the intracellular regions act in concert with the chemomechanical environment of the extracellular matrix and the molecular tumorigenic signaling pathways to effect malignant transformations. Results are presented to illustrate how changes to cytoskeletal architecture induced by cancer drugs and chemotherapy regimens can significantly influence cell mechanics and disease state. It is reasoned through experimental evidence that greater understanding of the mechanics of cancer cell deformability and its interactions with the extracellular physical, chemical and biological environments offers enormous potential for significant new developments in disease diagnostics, prophylactics, therapeutics and drug efficacy assays.
在过去十年中,关于细胞及亚细胞结构的生物力学和生物物理特性变化如何影响人类疾病的发生和发展以及如何受其影响的研究有了显著增长。本文概述了癌症细胞生物力学和生物物理学这一迅速发展的新兴研究领域。综述首先对癌细胞生物学以及肌动蛋白微丝、中间丝和微管生物聚合物细胞骨架成分在影响细胞力学、运动、分化和肿瘤转化中的作用进行了一些关键观察。为了为关于亚细胞结构改变、随之而来的细胞变形性、细胞粘附 细胞粘附、迁移、侵袭和肿瘤转移之间联系的机制讨论奠定基础,本文介绍了各种定量力学和物理检测方法,以提取癌细胞的弹性和粘弹性变形性。然后综述了文献中关于不同类型癌症细胞力学的现有结果。接下来展示了代表性案例研究,以说明化学诱导的细胞骨架变化、生物力学反应和来自细胞内区域的信号如何与细胞外基质的化学力学环境和分子致癌信号通路协同作用,从而实现恶性转化。展示的结果说明了癌症药物和化疗方案引起的细胞骨架结构变化如何能显著影响细胞力学和疾病状态。通过实验证据推断,对癌细胞变形性力学及其与细胞外物理、化学和生物环境相互作用的更深入理解为疾病诊断、预防、治疗和药物疗效检测的重大新进展提供了巨大潜力。