Schmidt Daniel, Bihr Timo, Fenz Susanne, Merkel Rudolf, Seifert Udo, Sengupta Kheya, Smith Ana-Sunčana
Institut für Theoretische Physik and Cluster of Excellence: Engineering of Advanced Materials, Friedrich Alexander Universität Erlangen-Nürnberg, 91052 Erlangen, Germany; II. Institut für Theoretische Physik, Universität Stuttgart, 70569 Stuttgart, Germany.
Institute of Complex Systems 7: Biomechanics, Forschungszentrum Jülich GmbH, 52425 Jülich, Germany; Lehrstuhl für Zell- und Entwicklungsbiologie (Zoologie I), Biozentrum der Universität Würzburg, 97074 Würzburg, Germany.
Biochim Biophys Acta. 2015 Nov;1853(11 Pt B):2984-91. doi: 10.1016/j.bbamcr.2015.05.025. Epub 2015 May 28.
The dynamics of formation of macromolecular structures in adherent membranes is a key to a number of cellular processes. However, the interplay between protein reaction kinetics, diffusion and the morphology of the growing domains, governed by membrane mediated interactions, is still poorly understood. Here we show, experimentally and in simulations, that a rich phase diagram emerges from the competition between binding, cooperativity, molecular crowding and membrane spreading. In the cellular context, the spontaneously-occurring organization of adhesion domains in ring-like morphologies is particularly interesting. These are stabilized by the crowding of bulky proteins, and the membrane-transmitted correlations between bonds. Depending on the density of the receptors, this phase may be circumvented, and instead, the adhesions may grow homogeneously in the contact zone between two membranes. If the development of adhesion occurs simultaneously with membrane spreading, much higher accumulation of binders can be achieved depending on the velocity of spreading. The mechanisms identified here, in the context of our mimetic model, may shed light on the structuring of adhesions in the contact zones between two living cells. This article is part of a Special Issue entitled: Mechanobiology.
粘附膜中大分子结构的形成动力学是许多细胞过程的关键。然而,由膜介导的相互作用所支配的蛋白质反应动力学、扩散与生长区域形态之间的相互作用,目前仍知之甚少。在此,我们通过实验和模拟表明,结合、协同性、分子拥挤和膜扩展之间的竞争产生了丰富的相图。在细胞环境中,粘附域以环状形态自发组织尤其有趣。这些通过大量蛋白质的拥挤以及键之间的膜传递相关性得以稳定。根据受体的密度,这个阶段可能会被规避,相反,粘附可能会在两个膜之间的接触区域均匀生长。如果粘附的发展与膜扩展同时发生,取决于扩展速度,可以实现更高的结合剂积累。在我们的模拟模型背景下确定的这些机制,可能有助于阐明两个活细胞之间接触区域中粘附结构的形成。本文是名为《机械生物学》的特刊的一部分。