London Centre for Nanotechnology, University College London, London, UK.
Department of Civil and Environmental Engineering, Politecnico di Milano, Milan, Italy.
Nat Mater. 2024 Nov;23(11):1563-1574. doi: 10.1038/s41563-024-02027-3. Epub 2024 Oct 28.
To fulfil their function, epithelial tissues need to sustain mechanical stresses and avoid rupture. Although rupture is usually undesired, it is central to some developmental processes, for example, blastocoel formation. Nonetheless, little is known about tissue rupture because it is a multiscale phenomenon that necessitates comprehension of the interplay between mechanical forces and biological processes at the molecular and cellular scales. Here we characterize rupture in epithelial monolayers using mechanical measurements, live imaging and computational modelling. 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. At large deformation, epithelia increase their stiffness multiple fold in a process controlled by a supracellular network of keratin filaments. Perturbing the keratin network organization fragilized the monolayers and prevented strain-stiffening. Although the kinetics of adhesive bond rupture ultimately control tissue strength, tissue rheology and the history of deformation set the strain and stress at the onset of fracture.
为了发挥其功能，上皮组织需要承受机械应力并避免破裂。尽管破裂通常是不希望发生的，但它是一些发育过程的核心，例如囊胚腔的形成。然而，由于它是一个多尺度现象，需要理解分子和细胞尺度上机械力和生物过程之间的相互作用，因此对组织破裂知之甚少。在这里，我们使用力学测量、实时成像和计算建模来描述上皮单层的破裂。我们表明，尽管仅由单层细胞组成，单层仍能承受惊人的大变形，通常在破裂前能容纳几倍的长度增加。在大变形时，上皮细胞的刚度会增加数倍，这个过程受角蛋白丝的超细胞网络控制。扰乱角蛋白网络组织会使单层变得脆弱，并阻止应变硬化。尽管粘合键断裂的动力学最终控制着组织的强度，但组织流变学和变形的历史决定了断裂起始时的应变和应力。
