Department of Biomedical Engineering, The University of Texas at Austin, Austin, Texas 78712, USA; email:
Department of Physics, The University of Texas at Austin, Austin, Texas 78712, USA.
Annu Rev Biophys. 2020 May 6;49:19-39. doi: 10.1146/annurev-biophys-121219-081637. Epub 2020 Jan 8.
Many critical biological events, including biochemical signaling, membrane traffic, and cell motility, originate at membrane surfaces. Each such event requires that members of a specific group of proteins and lipids rapidly assemble together at a specific site on the membrane surface. Understanding the biophysical mechanisms that stabilize these assemblies is critical to decoding and controlling cellular functions. In this article, we review progress toward a quantitative biophysical understanding of the mechanisms that drive membrane heterogeneity and organization. We begin from a physical perspective, reviewing the fundamental principles and key experimental evidence behind each proposed mechanism. We then shift to a biological perspective, presenting key examples of the role of heterogeneity in biology and asking which physical mechanisms may be responsible. We close with an applied perspective, noting that membrane heterogeneity provides a novel therapeutic target that is being exploited by a growing number of studies at the interface of biology, physics, and engineering.
许多关键的生物事件,包括生化信号、膜运输和细胞运动,都起源于膜表面。每一个这样的事件都需要特定蛋白质和脂质组的成员在膜表面的特定位置迅速聚集在一起。理解稳定这些组装体的生物物理机制对于解码和控制细胞功能至关重要。在本文中,我们回顾了在定量理解驱动膜异质性和组织的机制方面取得的进展。我们从物理角度出发,回顾了每个提出的机制背后的基本原理和关键实验证据。然后,我们转变为生物学角度,提出了异质性在生物学中的关键作用的例子,并询问哪些物理机制可能是负责的。最后,我们从应用角度指出,膜异质性提供了一个新的治疗靶点,越来越多的生物学、物理学和工程学交叉研究正在利用这一靶点。