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WIREs Syst Biol Med
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Systems biology of cellular membranes: a convergence with biophysics

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Systems biology and systems medicine have played an important role in the last two decades in shaping our understanding of biological processes. While systems biology is synonymous with network maps and ‘‐omics’ approaches, it is not often associated with mechanical processes. Here, we make the case for considering the mechanical and geometrical aspects of biological membranes as a key step in pushing the frontiers of systems biology of cellular membranes forward. We begin by introducing the basic components of cellular membranes, and highlight their dynamical aspects. We then survey the functions of the plasma membrane and the endomembrane system in signaling, and discuss the role and origin of membrane curvature in these diverse cellular processes. We further give an overview of the experimental and modeling approaches to study membrane phenomena. We close with a perspective on the converging futures of systems biology and membrane biophysics, invoking the need to include physical variables such as location and geometry in the study of cellular membranes. WIREs Syst Biol Med 2017, 9:e1386. doi: 10.1002/wsbm.1386

This article is categorized under:

  • Models of Systems Properties and Processes > Cellular Models
  • Biological Mechanisms > Cell Signaling
  • Models of Systems Properties and Processes > Mechanistic Models
The function of cellular membranes is tied closely to their geometry. Membranes are important not only for protecting the cytosolic components but also for organelle function and cytoskeletal remodeling. (a) Scanning electron microscopy (SEM) image of lamellipodia and filopodia in Aplysia growth cone (Reprinted with permission from Ref . Copyright 2015 ASCB); (b) Micrographs of clathrin‐mediated endocytosis at different stages of budding (Reprinted with permission from Ref . Copyright 1979 Company of Biologists Ltd.); (c) Membrane‐bound receptors, G‐protein coupled receptors, and receptor tyrosine kinases cause Ras GTPase activation at the plasma membrane and endomembranes (Reprinted with permission from Ref 35. Copyright 2007 John Wiley & Sons, Inc.); (d) Transmission electron microscopy (TEM) images of mitochondrial membrane in amoebae Chaos carolinensis show triply periodic minimal structures (Reprinted with permission from Ref . Copyright 1998 Springer‐Verlag); (e) TEM image of a nuclear membrane shaped as a catenoid by the nuclear pore complex (Reprinted from Ref. , with permission from Worner W. Franke and Ulrich Scheer); (f) Three‐dimensional (3D) reconstruction from SEM endoplasmic reticulum in an acinar cells of mouse salivary gland, showing stacks of parallel membrane sheets connected by helicoidal ramps. (Reprinted with permission from Ref . Copyright 2013 Elsevier Inc.)
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Different computational methods developed to study cellular membranes are valid in different length and time scales. Although some methods have attempted to bridge these scales, no unifying multiscale framework currently exists. This provides an opportunity for future model development.
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Model systems for the study of cellular membranes. In the top‐down approach, the cellular structural complexity is simplified to some or one of its parts by extracting membrane components from the cell. In the bottom‐up approach on the other hand, increasingly complex membrane systems are built up from synthetic materials.
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Membrane curvature can be induced by different mechanisms. (a) Owing to the tail and head chemistry, lipids can have cylindrical, conic, or reversed conic shapes, therefore inducing curvature when the lipid composition is different between the two lipid layers. (b) Large intrinsically curved proteins, such as BAR domain family of proteins, can scaffold and bend the membrane. (c) Insertion of amphipathic α‐helices in one leaflet induces membrane curvature. (d) Oligomerization of several monomers can scaffold and curve the membrane. (e) High surface concentration of membrane‐binding proteins produces a steric pressure that can bend the lipid bilayer.
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Biological membranes are complex in both lipid composition and protein inclusion, as illustrated by this schematic of a mammalian plasma membrane. Varying membrane composition can lead to a change in membrane thickness and other mechanical properties, which in turn affect their function.
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Models of Systems Properties and Processes > Mechanistic Models
Models of Systems Properties and Processes > Cellular Models
Biological Mechanisms > Cell Signaling

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