Babu Nandhu Krishna, Sreepadmanabh M, Dutta Sayantan, Bhattacharjee Tapomoy
<a href="https://ror.org/03gf8rp76">National Centre for Biological Sciences</a>, Tata Institute of Fundamental Research, Bangalore 560065, India.
Department of Chemical Engineering, <a href="https://ror.org/02qyf5152">Indian Institute of Technology Bombay</a>, Mumbai 400076, India.
Phys Rev E. 2024 Nov;110(5-1):054411. doi: 10.1103/PhysRevE.110.054411.
Wound healing is a complex biological process critical for maintaining an organism's structural integrity and tissue repair following an infection or injury. Recent studies have unveiled the mechanisms involving the coordination of biochemical and mechanical responses in the tissue in wound healing. In this article, we focus on the healing property of an epithelial tissue as a material while the effects of biological mechanisms such as cell proliferation, tissue intercalation, cellular migration, cell crawling, and filopodia protrusion is minimal. We present a mathematical framework that predicts the fate of a wounded tissue based on the wound's geometrical features and the tissue's mechanical properties. Precisely, adapting the vertex model of tissue mechanics, we predict whether a wound of a specific size in an epithelial monolayer characterized by certain levels of actomyosin contractility and cell-cell adhesion will heal (i.e., close), shrink in size, or rupture the tissue further. Moreover, we show how tissue-mediated mechanisms such as purse-string tension at the wound boundary facilitate wound healing. Finally, we validate the predictions of our model by designing an experimental setup that enables us to create wounds of specific sizes in kidney epithelial cells (MDCK) monolayers. Altogether, this work sets up a basis for interpreting the interplay of mechanical and geometrical features of a tissue in the process of wound healing.
伤口愈合是一个复杂的生物学过程，对于维持生物体的结构完整性以及在感染或受伤后的组织修复至关重要。最近的研究揭示了伤口愈合过程中组织内生化和机械反应协同作用的机制。在本文中，我们关注上皮组织作为一种材料的愈合特性，而细胞增殖、组织嵌入、细胞迁移、细胞爬行和丝状伪足突出等生物学机制的影响极小。我们提出了一个数学框架，该框架基于伤口的几何特征和组织的力学特性来预测受伤组织的命运。具体而言，通过调整组织力学的顶点模型，我们预测在以一定水平的肌动球蛋白收缩性和细胞间黏附为特征的上皮单层中，特定大小的伤口是否会愈合（即闭合）、尺寸缩小或进一步使组织破裂。此外，我们展示了诸如伤口边界处的荷包缝合张力等组织介导的机制如何促进伤口愈合。最后，我们通过设计一个实验装置来验证我们模型的预测，该装置使我们能够在肾上皮细胞（MDCK）单层中制造特定大小的伤口。总之，这项工作为解释伤口愈合过程中组织的力学和几何特征之间的相互作用奠定了基础。
