Rupture Strength of Living Cell Monolayers
Rupture Strength of Living Cell Monolayers
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活细胞单层的断裂强度
DOI：
10.1101/2023.01.05.522736
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Duque J
中科院分区：
文献类型：
--
作者：
Duque J
组织承受机械应力和避免断裂的能力是其功能的基本支柱。响应生理水平的应激而发生的骨折可能是不受欢迎的，例如由疾病或基因突变引起，或者是发育过程的一个组成部分，例如在小鼠囊胚腔形成期间或在果蝇腿部外翻期间。尽管它很重要，但我们对细胞组织的断裂知之甚少，因为它是一个多尺度的过程，需要理解机械力与分子和细胞尺度上的过程之间的相互作用。通过结合机械测量、实时成像和计算建模，我们描述了单层上皮的断裂特征。我们发现，尽管仅由单层细胞组成，但单层细胞可以承受令人惊讶的大变形，在破裂前通常可以容纳其长度增加数倍。为了防止大变形，上皮细胞在角蛋白中间丝控制的过程中将其硬度增加数倍。扰动角蛋白组织使单层细胞脆弱并防止应变硬化。使用计算方法，我们表明，虽然键断裂的动力学最终控制断裂，但组织流变学和失效前的变形历史设定了组织在断裂开始时达到的应变和应力。我们的数据描绘了上皮细胞作为多功能材料的画面，在低应变率下将抗冲击性与可变形性结合起来。
The ability of tissues to sustain mechanical stress and avoid fracture is a fundamental pillar of their function. Fracture in response to physiological levels of stress can be undesired, for example resulting from disease or genetic mutations, or be an integral part of developmental processes, such as during blastocoel formation in mouse or during leg eversion in flies. Despite its importance, we know very little about fracture in cellularised tissues because it is a multi-scale process that necessitates comprehension of the interplay between mechanical forces and processes at the molecular and cellular scales. Using a combination of mechanical measurements, live imaging and computational modelling, we characterise fracture in epithelial monolayers. We show that, despite consisting of only a single layer of cells, monolayers can withstand surprisingly large deformations, often accommodating several-fold increases in their length before rupture. To protect against large deformation, epithelia increase their stiffness multiple-fold in a process controlled by keratin intermediate filaments. Perturbing keratin organisation fragilised monolayers and prevented strain stiffening. Using computational approaches, we show that, although the kinetics of bond rupture ultimately control fracture, tissue rheology and the history of deformation prior to failure set the strain and stress that the tissue reaches at the onset of fracture. Our data paint a picture of epithelia as versatile materials that combine resistance to shocks with deformability when subjected to low strain rates.