Capturing the mechanosensitivity of cell proliferation in models of epithelium

• 成果类型: Article
• 署名作者: Hoellring, Kevin; Nuic, Lovro; Rogic, Luka; Kaliman, Sara; Gehrer, Simone; Wollnik, Carina; Rehfeldt, Florian; Hubert, Maxime; Smith, Ana-Suncana
• 署名单位: University of Erlangen Nuremberg; Rudjer Boskovic Institute; University of Gottingen; University of Bayreuth
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-10422
• DOI: 10.1073/pnas.2308126121
• 发表日期: 2024-11-05
• 关键词: beta-catenin activation; single-cell; GROWTH; division; tissues; stress

摘要

Despite the primary role of cell proliferation in tissue development and homeostatic maintenance, the interplay between cell density, cell mechanoresponse, and cell growth and division is not yet understood. In this article, we address this issue by reporting on an experimental investigation of cell proliferation on all time- and length-scales of the development of a model tissue, grown on collagen-coated glass or deformable substrates. Through extensive data analysis, we demonstrate the relation between mechanoresponse and probability for cell division, as a function of the local cell density. Motivated by these results, we construct a minimal model of cell division in tissue environment that can recover the data. By parameterizing the growth and the dividing phases of the cell cycle, and introducing such a proliferation model in dissipative particle dynamics simulations, we recover the mechanoresponsive, time- dependent density profiles in 2D tissues growing to macroscopic scales. The importance of separating the cell population into growing and dividing cells, each characterized by a particular time scale, is further emphasized by calculations of density profiles based on adapted Fisher-Kolmogorov equations. Together, these results show that the mechanoresponse on the level of a constitutive cell and its proliferation results in a matrix-sensitive active pressure. The latter evokes massive cooperative displacement of cells in the invading tissue and is a key factor for developing large-scale structures in the steady state.